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Background: Prostate cancer (PCa) presents a wide spectrum. Systemic immune-inflammation index (SII) and Ki-67 index are new biomarkers that can predict prognosis in different types of cancer. We explored the predictive value of their combination on the prognosis of PCa patients after laparoscopic radical prostatectomy (LRP). Methods: In this retrospective study, 290 patients who underwent LRP at Nanjing Lishui People's Hospital between January 2016 and February 2021 were enrolled. They were divided into the good prognosis group (N = 235) and poor prognosis group (N = 55) based on the follow-up results. Both the baseline data and postoperative pathological results were collected. The Ki-67 index was determined using immunohistochemical kits, and the patients were allocated to the SII/Ki-67 index high/low expression groups according to the cut-off values to further analyze their relationship with clinical/pathological data of PCa patients. Logistics multivariate regression analysis was utilized to analyze the independent factors affecting post-LRP prognosis of CPa patients. ROC curve was plotted to assess the predictive value for post-LRP prognosis, and Kaplan-Meier curve/Log-rank were used for analysis. Results: Significant differences were found in PSA/Gleason score/T stage/lymph node metastasis/seminal vesicle invasion/neutrophils/lymphocytes/platelets/preoperative SII/Ki-67 index between the good/poor prognosis groups. Preoperative SII/Ki-67 were related to PSA/lymphocytes/platelets in PCa. Seminal vesicle invasion and preoperative SII + Ki-67 index were independent factors affecting post-LRP prognosis. Preoperative SII + Ki-67 index had a better predictive value than preoperative SII or Ki-67 index alone. Patients with high preoperative SII and Ki-67 index levels had an increased risk of poor prognosis after LRP. Conclusion: Preoperative SII + Ki-67 index had a better predictive value for poor prognosis after LRP than SII or Ki-67 index alone. [ABSTRACT FROM AUTHOR]

Purpose: Retroperitoneal liposarcoma (RLPS) poses a challenging scenario for surgeons due to its unpredictable biological behavior. Surgery remains the primary curative option for RLPS; however, the need for additional information to guide surgical strategies persists. Volume-based 18F-FDG PET/CT may solve this issue. Methods: We analyzed data from 89 RLPS patients, measuring metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum standardized uptake value (SUVmax) and explored their associations with clinical, prognostic, and pathological factors. Results: MTV, TLG of multifocal and recurrent RLPS were significantly higher than unifocal and primary ones (P < 0.001, P < 0.001, P = 0.003 and P = 0.002, respectively). SUVmax correlated with FNCLCC histological grade, mitotic count and Ki-67 index (P for G1/G2 = 0.005, P for G2/G3 = 0.017, and P for G1/G3 = 0.001, P < 0.001 and P = 0.024, respectively). MTG, TLG and SUVmax of WDLPS were significantly lower than DDLPS and PLPS (P for MTV were 0.009 and 0.022, P for TLG were 0.028 and 0.048, and P for SUVmax were 0.027 and < 0.001, respectively). Multivariable Cox analysis showed that MTV > 457.65 (P = 0.025), pathological subtype (P = 0.049) and FNCLCC histological grade (P = 0.033) were related to overall survival (OS). Conclusions: Our findings indicate that MTV is an independent prognostic factor for RLPS, while MTV, TLG, and SUVmax can preoperatively predict multifocal lesions, histological grade, and pathological subtype. Volume-based 18F-FDG PET/CT offers valuable information to aid in the decision-making process for RLPS surgical strategies. [ABSTRACT FROM AUTHOR]

Introduction: The early identification of good responders to neoadjuvant chemotherapy (NACT) holds a significant potential in the optimal treatment of breast cancer. A recent Bayesian approach has been postulated to improve the accuracy of the intravoxel incoherent motion (IVIM) model for clinical translation. This study examined the prediction and early sensitivity of Bayesian IVIM to NACT response. Materials and methods: Seventeen female patients with breast cancer were scanned at baseline and 16 patients were scanned after Cycle 1. Tissue diffusion and perfusion from Bayesian IVIM were calculated at baseline with percentage change at Cycle 1 computed with reference to baseline. Cellular proliferative activity marker Ki-67 was obtained semi-quantitatively with percentage change at excision computed with reference to core biopsy. Results: The perfusion fraction showed a significant difference (p = 0.042) in percentage change between responder groups at Cycle 1, with a decrease in good responders [−7.98% (−19.47–1.73), n = 7] and an increase in poor responders [10.04% (5.09–28.93), n = 9]. There was a significant correlation between percentage change in perfusion fraction and percentage change in Ki 67 (p = 0.042). Tissue diffusion and pseudodiffusion showed no significant difference in percentage change between groups at Cycle 1, nor was there a significant correlation against percentage change in Ki-67. Perfusion fraction, tissue diffusion, and pseudodiffusion showed no significant difference between groups at baseline, nor was there a significant correlation against Ki-67 from core biopsy. Conclusion: The alteration in tumour perfusion fraction from the Bayesian IVIM model, in association with cellular proliferation, showed early sensitivity to good responders in NACT. [ABSTRACT FROM AUTHOR]

To validate a radiomics model based on multi-sequence magnetic resonance imaging (MRI) in predicting the ki-67 expression levels in early-stage endometrial cancer, 131 patients with early endometrial cancer who had undergone pathological examination and preoperative MRI scan were retrospectively enrolled and divided into two groups based on the ki-67 expression levels. The radiomics features were extracted from the T2 weighted imaging (T2WI), dynamic contrast enhanced T1 weighted imaging (DCE-T1WI), and apparent diffusion coefficient (ADC) map and screened using the Pearson correlation coefficients (PCC). A multi-layer perceptual machine and fivefold cross-validation were used to construct the radiomics model. The receiver operating characteristic (ROC) curves analysis, calibration curves, and decision curve analysis (DCA) were used to assess the models. The combined multi-sequence radiomics model of T2WI, DCE-T1WI, and ADC map showed better discriminatory powers than those using only one sequence. The combined radiomics models with multi-sequence fusions achieved the highest area under the ROC curve (AUC). The AUC value of the validation set was 0.852, with an accuracy of 0.827, sensitivity of 0.844, specificity of 0.773, and precision of 0.799. In conclusion, the combined multi-sequence MRI based radiomics model enables preoperative noninvasive prediction of the ki-67 expression levels in early endometrial cancer. This provides an objective imaging basis for clinical diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Mast cell tumor (MCT) is a common skin cancer in dogs that has a wide range of clinical behaviors. The purpose of this study was to develop a novel multicolor flow cytometry (FC) panel that will enable the quantification of candidate prognostic markers (Ki-67 and pKIT) in fine needle aspirate (FNA) samples prior to surgical removal of the tumors. FNA of canine MCTs and the NI-1 cell line were utilized to develop a FC panel that includes a viability dye (FVS620, BD Biosciences; 7-AAD, Invitrogen) and the following primary conjugated antibodies: CD117-PE (ACK45, BD Biosciences), pKIT-A647 (polyclonal bs-3242R, BIOSS) and Ki-67- FITC (20Raj1, eBioscience; MIB-1, DAKO). A total of nine FNA samples of canine MCTs were collected, seven out which produced sufficient cells for FC analysis. The Ki-67 antibody clone 20Raj1 produced a positive signal when applied to blood leukocytes but failed to provide robust labeling of neoplastic mast cells. The Ki-67 antibody clone MIB-1 delivered a superior staining quality in both the NI-1 cells and primary MCT cells. CD117-PE signal was adequate post fixation and permeabilization and in the combination of 7-AAD. pKIT produced non-specific staining and was not suitable for this multicolor FC panel. In conclusion, FNA samples of canine MCTs can often yield adequate cell numbers for FC analysis, and a multicolor FC panel was developed that can detect Ki-67 in canine mast cells. This would permit further studies into the potential use of this panel for canine cutaneous and subcutaneous MCT prognostication purposes. [ABSTRACT FROM AUTHOR]

Objective: To investigate the prognostic prediction of a new indicator, combined by tumor grade and Ki-67, in patients with resected pancreatic ductal adenocarcinoma (PDAC). Methods: Data were retrospectively collected from consecutive patients who underwent primary resection of pancreas from December 2012 to December 2017. Tumor grade and Ki-67 were reviewed from routine pathological reports. G-Ki67 was classified as three categories as I (G1/2 and Ki-67 < 40%), II (G1/2 and Ki-67 ≥ 40%), and III(G3/4 and all Ki-67). Results: Cox regression analyses revealed that tumor stage (II vs. I: hazard ratio (HR), 3.781; 95% confidence index (CI), 2.844–5.025; P < 0.001; III vs. I: HR, 7.476; 95% CI, 5.481–10.20; P < 0.001) and G-Ki67 (II vs. I: HR, 1.299; 95% CI, 1.038–1.624; P = 0.022; III vs. I: HR, 1.942; 95% CI, 1.477–2.554; P < 0.001) were independent prognostic factors in the developing cohort. The result was rectified in the validation cohort. In subgroups analysis, G-Ki67 (II vs. I: HR, 1.866 ; 95% CI, 1.045–3.334; P = 0.035; III vs. I: HR, 2.333 ; 95% CI, 1.156–4.705; P = 0.018) also had a high differentiation for survival prediction. Conclusion: Our findings indicate that three-categories of G-Ki67 in resectable PDAC according to the routine pathological descriptions provided additional prognostic information complementary to the TNM staging system. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) infection is a major health problem worldwide and its eradication is mandatory. Direct acting HCV polymerase inhibitors, such as Sofosbuvir (SOF), is an effective regimen. However, it has some side effects like mutagenesis, carcinogenesis, and the impairment of testicular function. It is important to evaluate the safety of SOF on the ovary, as there are no studies yet. Increasing the production of Reactive Oxygen Species (ROS), causes oxidative stress, which affects ovulation process, female reproduction, and fertility. Accumulation of SOF in the cells was demonstrated to promote ROS generation. Vitamin E (Vit E) is an antioxidant agent that has an essential role in the female reproductive system, its deficiency can cause infertility. We explored the effect of SOF treatment alone and co-treated with Vit E on ovarian ROS level and ovarian morphology experimentally using biochemical and immunohistochemical studies. Significant changes in oxidative stress markers; nitric oxide and malondialdehyde lipid peroxidation, antioxidant enzymes; catalase, super oxide dismutase, and reduced glutathione, proliferating markers; proliferation cell nuclear antigen and Ki-67 antigen and caspase 3 apoptotic marker were demonstrated. It was shown that where SOF induced oxidative stress, it also aggravated ovarian dysfunction. The essential role of Vit E as an antioxidant agent in protecting the ovarian tissue from the effect of oxidative stress markers and preserving its function was also displayed. This could be guidance to add Vit E supplements to SOF regimens to limit its injurious effect on ovarian function. [ABSTRACT FROM AUTHOR]

Background: Up to now, endometrial cancer (EC) treatments are mainly represented by surgery followed by adjuvant chemotherapy or radiotherapy. The updated guidelines give a 2A recommendation for the use of hormone therapy only in advanced low-grade ECs, underlying the need for more data on the role of hormone therapy in the adjuvant setting. Methods: The clinicopathological data of 158 early-stage EC patients was retrospectively collected. A Ki-67 cut-off value of 40% was established based on literature data. Disease-free survival (DFS) and Overall survival (OS) were evaluated. Results: Results: Multivariate analysis of DFS and OS showed a significantly increased risk of progression in patients with >40% Ki-67 [HR = 3.13 (95% CI; 1.35–7.14); p = 0.007] and a significantly higher relative risk of death [HR = 3.70 (95% CI; 1.69–8.33); p = 0.001]. The predictive role of the Ki-67 index was highlighted by the clinical benefit of adjuvant hormone in patients with high Ki-67. Conclusions: Our results suggest a positive role of the Ki-67 index as a prognostic and potentially predictive marker in EC, although further studies are warranted to reach a definitive conclusion. [ABSTRACT FROM AUTHOR]

Background: Endometrial cancer is one of the common gynecologic cancer and accounts for nearly 5% of cancer cases and more than 2% of deaths due to cancer in women worldwide.Bcl-2 is an anti-apoptotic gene involved in the regulation of apoptosis and Ki-67 is a recognized indicator of cell mitotic activity. Increased expression of both indicates tumorigenesis. Analyzing the expression of these markers in cyclical endometrium, endometrial hyperplasia and in endometrial carcinoma will help in the development of new treatment modalities specific against these markers. Aim and objectives: To evaluate the expression of Bcl-2 and Ki-67 in endometrial lesions and to compare the pattern of expression of Bcl-2 and Ki-67 in different endometrial lesions and in cyclical endometrium. Methods: Hospital based observational, cross- sectional study was conducted in 57 patient of different cyclical endometrium and endometrium lesions. The selected tissue blocks were processed for hematoxylin and eosin stain and IHC staining for Bcl-2 and Ki-67. Results: In this study, 11 cases of proliferative endometrium and 9 cases of secretory endometrium were studied. Mean Bcl-2 score was 7.6 in proliferative phase and 1.3 in secretory phase whereas mean Ki-67 score was 7.27 in proliferative phase and 2.4 in secretory phase. In this study 10 cases of Disordered proliferative phase showed mean score 11.2 of Bcl-2 that was slightly higher than hyperplasia which has Bcl-2 score of 6.2. Of the total 12 cases of hyperplasia 9 cases were of simple hyperplasia and 3 were of atypical hyperplasia. In simple hyperplasia mean score was 6.2 for Bcl2 and 4.8 for Ki-67. In atypical hyperplasia mean score was 4 for Bcl-2 and 2.6 for Ki- 67. Conclusions: Bcl-2 and Ki-67 have been found to be reliable markers to indicate the progression of the disease and might be a novel indication for treatment and follow-up. [ABSTRACT FROM AUTHOR]

Background: Preoperative differentiation of atypical meningioma (AtM) from transitional meningioma (TrM) is critical to clinical treatment. Purpose: To investigate the role of apparent diffusion coefficient (ADC) histogram analysis in differentiating AtM from TrM and its correlation with the Ki-67 proliferation index (PI). Methods: Clinical, imaging, and pathological data of 78 AtM and 80 TrM were retrospectively collected. Regions of interest (ROIs) were delineated on axial ADC images using MaZda software and histogram parameters (mean, variance, skewness, kurtosis, 1st percentile [ADCp1], 10th percentile [ADCp10], 50th percentile [ADCp50], 90th percentile [ADCp90], and 99th percentile [ADCp99]) were generated. The Mann–Whitney U test was used to compare the differences in histogram parameters between the two groups; receiver operating characteristic (ROC) curves were used to assess diagnostic efficacy in differentiating AtM from TrM preoperatively. The correlation between histogram parameters and Ki-67 PI was analyzed. Results: All histogram parameters of AtM were lower than those of TrM, and the variance, skewness, kurtosis, ADCp90, and ADCp99 were significantly different (P < 0.05). Combined ADC histogram parameters (variance, skewness, kurtosis, ADCp90, and ADCp99) achieved the best diagnostic performance for distinguishing AtM from TrM. Area under the curve (AUC), sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 0.800%, 76.25%, 67.95%, 70.15%, 70.93%, and 73.61%, respectively. All histogram parameters were negatively correlated with Ki-67 PI (r = −0.012 to −0.293). Conclusion: ADC histogram analysis is a potential tool for non-invasive differentiation of AtM from TrM preoperatively, and ADC histogram parameters were negatively correlated with the Ki-67 PI. [ABSTRACT FROM AUTHOR]

Background: Neuroendocrine tumors (NETs) represent a diverse group of neoplasms that arise from neuroendocrine cells, with Ki-67 immunostaining serving as a crucial biomarker for assessing tumor proliferation and prognosis. Accurate and reliable quantification of Ki-67 labeling index is essential for effective clinical management.Methods: We aimed to evaluate the performance of open-source/open-access deep learning cloud-native platform, DeepLIIF (https://deepliif.org), for the quantification of Ki-67 expression in gastrointestinal neuroendocrine tumors and compare it with the manual quantification method.Results: Our results demonstrate that the DeepLIIF quantification of Ki-67 in NETs achieves a high degree of accuracy with an intraclass correlation coefficient (ICC) = 0.885 with 95% CI (0.848– 0.916) which indicates good reliability when compared to manual assessments by experienced pathologists. DeepLIIF exhibits excellent intra- and inter-observer agreement and ensures consistency in Ki-67 scoring. Additionally, DeepLIIF significantly reduces analysis time, making it a valuable tool for high-throughput clinical settings.Conclusion: This study showcases the potential of open-source/open-access user-friendly deep learning platforms, such as DeepLIIF, for the quantification of Ki-67 in neuroendocrine tumors. The analytical validation presented here establishes the reliability and robustness of this innovative method, paving the way for its integration into routine clinical practice. Accurate and efficient Ki-67 assessment is paramount for risk stratification and treatment decisions in NETs and AI offers a promising solution for enhancing diagnostic accuracy and patient care in the field of neuroendocrine oncology. [ABSTRACT FROM AUTHOR]

Osteosarcoma (OS) is the most prevalent primary bone cancer, with a high morbidity and mortality rate. Over the past decades, therapeutic approaches have not considerably improved patients' survival rates, and further research is required to find efficient treatments for OS. Data from several studies have shown that urolithin B (UB), the intestinal metabolite of polyphenolic ellagitannins, is emerging as a new class of anticancer compounds, yet its effect on OS cancer cells remains elusive. Herein, we investigated UB's antimetastatic, antiproliferative, and apoptotic effects on the MG‐63 OS cell line. Cell viability assay, annexin V/propidium iodide staining, cell cycle arrest analysis, determination of the gene expression of MMP‐2, MMP‐9, Bax, Bcl‐2, and p53 messenger RNA (mRNA), evaluation of reactive oxygen species (ROS) generation and migration, and MMP‐2 and MMP‐9 protein expression assessments were performed. UB caused late apoptosis, necrosis, G2/M arrest, and ROS generation in MG‐63 cells. It increased the mRNA expression of the p53 tumor suppressor and Bax proapoptotic genes. UB also inhibited the migration and metastatic behavior of MG‐63 OS cells by downregulating mRNA and MMP‐2 and MMP‐9 protein expression. In general, although further in vivo investigations are warranted, the current results showed that UB might be utilized as a potential novel natural compound for OS therapy due to its nontoxic, antiproliferative, and antimetastatic nature. [ABSTRACT FROM AUTHOR]

The pathologic evaluation of a tumor tissue is an essential part of an acromegaly patient's assessment. This study aimed to analyze the pathologic characteristics of pituitary tumors in patients with acromegaly. The demographic data, in addition to the hormonal, imaging, and pathologic results of 120 patients with acromegaly after pituitary surgery, were extracted from the Polish Acromegaly Registry. We compared sparsely and densely granulated tumors, GH(+), mixed GH(+)/PRL(+) and plurihormonal tumors, α-subunit-positive and α-subunit-negative tumors, and tumors of various Ki-67 indices in terms of the abovementioned features. Sparsely granulated tumors were more frequent in women than in men (p = 0.001) and in younger patients (p = 0.011), and they were larger (p < 0.001) compared to densely granulated tumors. Tumors with positive α-subunit were smaller (p = 0.013), showed extrasellar extension less often (p = 0.039), and were more often densely granulated (p < 0.001) compared to α-subunit-negative tumors. Patients with a higher Ki-67 index were younger (p < 0.001) and more often diagnosed with genetic syndromes (p = 0.02); they had higher GH concentrations (p = 0.007), larger tumors (p = 0.006), and cavernous sinus invasions more frequently (p = 0.022). Conclusions: The pathologic characteristics of somatotroph pituitary tumors are associated with patient's age, sex, hormonal results, tumor size, and the degree of extrasellar expansion. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor (EGFR) has emerged as an important therapeutic target in many cancers, and overexpression of EGFR is frequently observed in hepatocellular carcinomas (HCCs). Near‐infrared photoimmunotherapy (NIR‐PIT) is a new anticancer treatment that selectively damages the cell membrane of cancer cells after NIR light‐induced photochemical reaction of IR700, which is bound to a targeting antibody on the cell membrane. NIR‐PIT using cetuximab‐IR700 has already been approved in Japan, is under review by the US Food and Drug Administration (FDA) for advanced head and neck cancers, and its safety has been established. However, EGFR has not been investigated as a target in NIR‐PIT in HCCs. Here, we investigate the application of NIR‐PIT using cetuximab‐IR700 to HCCs using xenograft mouse models of EGFR‐expressing HCC cell lines, Hep3B, HuH‐7, and SNU‐449. In vitro NIR‐PIT using EGFR‐targeted cetuximab‐IR700 killed cells in a NIR light dose‐dependent manner. In vivo NIR‐PIT resulted in a delayed growth compared with untreated controls. In addition, in vivo NIR‐PIT in both models showed histological signs of cancer cell damage, such as cytoplasmic vacuolation and nuclear dysmorphism. A significant decrease in Ki‐67 positivity was also observed after NIR‐PIT, indicating decreased cancer cell proliferation. This study suggests that NIR‐PIT using cetuximab‐IR700 has potential for the treatment of EGFR‐expressing HCCs. [ABSTRACT FROM AUTHOR]

Background: Intrahepatic cholangiocarcinoma (iCCA) is an aggressive primary liver cancer with dismal outcome, high Ki-67 expression is associated with active progression and poor prognosis of iCCA, the application of MRE in the prediction of iCCA Ki-67 expression has not yet been investigated until now. We aimed to evaluate the value of magnetic resonance elastography (MRE) in assessing Ki-67 expression for iCCA. Results: In the whole cohort, 97 patients (57 high Ki-67 and 40 low Ki-67; 58 males, 39 females; mean age, 58.89 years, ranges 36–70 years) were included. At the multivariate analysis, tumor stiffness (odds ratio (OR) = 1.669 [95% CI: 1.307–2.131], p < 0.001) and tumor apparent diffusion coefficient (ADC) (OR = 0.030 [95% CI: 0.002, 0.476], p = 0.013) were independent significant variables associated with Ki-67. Areas under the curve of tumor stiffness for the identification of high Ki-67 were 0.796 (95% CI 0.702, 0.871). Tumor stiffness was moderately correlated with Ki-67 level (r = 0.593, p < 0.001). When both predictive variables of tumor stiffness and ADC were integrated, the best performance was achieved with area under the curve values of 0.864 (95% CI 0.780–0.926). Conclusion: MRE-based tumor stiffness correlated with Ki-67 in iCCA and could be investigated as a potential prognostic biomarker. The combined model incorporating both tumor stiffness and ADC increased the predictive performance. Critical relevance statement: MRE-based tumor stiffness might be a surrogate imaging biomarker to predict Ki-67 expression in intrahepatic cholangiocarcinoma patients, reflecting tumor cellular proliferation. The combined model incorporating both tumor stiffness and apparent diffusion coefficient increased the predictive performance. Key points: • MRE-based tumor stiffness shows a significant correlation with Ki-67. • The combined model incorporating tumor stiffness and apparent diffusion coefficient demonstrated an optimized predictive performance for Ki-67 expression. • MRE-based tumor stiffness could be investigated as a potential prognostic biomarker for intrahepatic cholangiocarcinoma. [ABSTRACT FROM AUTHOR]

Background: Glioma is one of the most malignant tumors, which leads to high mortality in cancer patients. At present, there is no effective therapy for glioma. Therefore, it is urgent and necessary to find new molecular targets for anti-glioma therapy. Objective: The present study aimed to investigate the role of signal transducer and activator of transcription 1 (STAT1) in the development and progression of human glioma and related mechanisms. Methods: According to the instructions of Lipofectamine TM2000 transfection reagent, we transiently transfected the plasmid pcDNA3.1-STAT1 into glioma U251 cells. Then STAT1 expression in glioma U251 and LN382 cells was detected by Western blot. MTT was performed to assay the proliferative activity of U251 cells after STAT1 transduction, flow cytometry was used to detect cell cycle and apoptosis indicators, cell migration indicator was determined by Wound healing, and Western blot was used for detecting the expression level and change trend of p53, p21, bcl-2, Caspase-8, Cyclin A and Cyclin E in transfected cells. Results: Overexpressed STAT1 significantly inhibited U251 cell proliferation and promoted U251 cell apoptosis. Meanwhile, high expression of STAT1 can increase the expression of p53, p21, and Caspase-8 while inhibiting the expression of bcl-2, Cyclin A, and Cyclin E. Conclusion: Highly expressed STAT1 inhibits the proliferative activity of human glioma U251 cells and can promote tumor cell apoptosis and block cell cycle progression while regulating the expression of various signal transduction molecules. Thus, STAT1 has a critical function in the development and progression of glioma and is a novel target for glioma therapy. [ABSTRACT FROM AUTHOR]

We present an informative case of a relatively young patient in which it was accidentally discovered a serous tubal intraepithelial carcinoma, after a hysterectomy with bilateral salpingectomy for a benign condition. The diagnosis was substantiated by immunomarkers p53 and Ki-67. Our case supports the concept that salpingectomy can be performed at the time of benign gynecological surgeries. It is a simple and rapid procedure that can be done with ease and does not influence the overall status of the patient. In terms of complications, it appears to be safe, as it does not increase them. The examination of the fallopian tubes samples is important, as serous tubal intraepithelial carcinoma (STIC) is one of the precursor lesions of the high-grade pelvic serous carcinoma. The mechanism of STIC development is yet neither fully understood, nor described. The investigation of p53 and Ki-67 are part of the immunohistochemistry workup that brings more information about the disease. Women who achieved reproduction and undergo pelvic surgery are recommended to have both fallopian tubes removed, but the decision should be taken by the patient, based on the benefits and risks that the medical team must explain before the procedure. [ABSTRACT FROM AUTHOR]

Purpose: The sensitivity of [18F] fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) for detecting hepatocellular carcinoma (HCC) has not been clarified thoroughly. Our study seeks to explore the association between the Ki-67 index and FDG-avidity in HCC tumors using 18F-FDG PET/CT. Methods: 112 HCC lesions from 109 patients detected by 18F-FDG PET/CT were included retrospectively between August 2017 and May 2022, comprising 82 lesions in the training cohort and 30 in the validation cohort to simulate prospective studies. In the training cohort, lesions were stratified by a lesion-to-liver maximum standardized uptake value (SUVmax) ratio cut-off of 1.59. The relationships between lesion-to-liver SUVmax ratios and several clinical factors including tumor differentiation, alpha fetoprotein (AFP), carcinoembryonic antigen (CEA), hepatitis B virus (HBV) infection, Ki-67 index et al. were assessed. These findings were subsequently validated in the independent validation cohort. Results: In the training cohort, group A1 lesions demonstrated a higher Ki-67 index (%, 40.00 [30.00, 57.50] vs. 10.00 [5.00, 28.75], p<0.001) than group A0, the positive correlation between FDG-avidity and Ki-67 index was revealed by multivariate analysis, OR=1.040, 95% CI of OR [1.004–1.077], p=0.030. The calculated cut-off value was 17.5% using the receiver operating characteristic (ROC) curve, with an area under curve (AUC) of 0.834 and 95% CI [0.742–0.926], p<0.001. These findings were further validated in the independent validation cohort, with similar results (AUC=0.875, 95% CI [0.750–1.000], p<0.001). Conclusion: In comparison to tumor differentiation, Ki-67 index demonstrates a stronger association with FDG-avidity in HCC tumors, and when the Ki-67 index exceeds 17.5%, 18F-FDG PET/CT might serve as a useful indicator for HCC. [ABSTRACT FROM AUTHOR]

Objective: To study the value of radiomics models based on plain and multiphase contrast-enhanced CT to predict Ki-67 expression in gastrointestinal stromal tumors (GISTs). Methods: A total of 215 patients with GISTs were retrospectively analyzed, including 150 patients in one hospital as the training set and 65 patients in another hospital as the external verification set. The tumor at the largest level of CT images was delineated as the region of interest (ROI). The maximum diameter of the ROI was defined as the tumor size. A total of 851 radiomics features were extracted from each ROI by 3D Slicer Radiomics. After dimensionality reduction, three machine learning classification algorithms including logistic regression (LR), random forest (RF), and support vector machine (SVM) were used for Ki-67 expression prediction. Using a multivariable logistic model, a nomogram was established to predict the expression of Ki-67 individually. Results: Delong tests showed that the SVM models had the highest accuracy in the arterial phase (Z value 0.217–1.139) and venous phase (Z value 0.022–1.396). For the plain phase, LR and SVM models had the highest accuracy (Z value 0.874–1.824, 1.139–1.763). For the delayed phase, LR models had the highest accuracy (Z value 0.056–1.824). For the combined phase, RF models had the highest accuracy (Z value 0.232–1.978). There was no significant difference among the above models for KI-67 expression prediction (Z value 0.022–1.978). A nomogram was developed with a C-index of 0.913 (95% CI, 0.878 to 0.956). Conclusions: Radiomics of both plain and enhanced CT images could accurately predict the expression of Ki-67 in GIST. For patients who were not suitable to use contrast agents, plain scan could be used as an alternative. Clinical relevance statement: CT radiomics could accurately predict the expression of Ki-67 in GIST, which has a great clinical value in reflecting the proliferative activity of tumor cells and helping determine whether a patient is suitable for adjuvant therapy with imatinib. Key Points: • Radiomics of both plain and enhanced CT images could accurately predict the expression of Ki-67 in GIST. • For patients who were not suitable to use contrast agents, plain scan could be used as an alternative. • A radiomics nomogram was developed to allow personalized preoperative evaluation with high accuracy. [ABSTRACT FROM AUTHOR]

• The DRD2 expression is regulated by its promoter region upstream factors or methylation status. • Cancer cell proliferation improved the upregulation of DRD2 and decreased DRD2's downregulation. • DRD2 plays a critical role in the FLNA-ERK signaling pathway. • DRD2 gene is hypomethylated in hormone-receptor-negative breast cancer or it's high-risk factor. We investigated the effect of stem cell marker dopamine receptor D2 (DRD2) on the proliferation of hormone-receptor-negative breast cancer cells. High-throughput DNA methylation sequencing on an 850 K chip was used to pre-screen breast cancer tissues with significant methylation differences. The expression of DRD2 in breast cancer and normal breast tissues, and clinical risk factors, were detected by pyrophosphoric acid validation and immunohistochemistry. In vitro and in vivo experiments verified the possible molecular signaling pathways. DRD2 promoter region was hypomethylated in hormone-receptor-negative breast cancer or with high-risk factors compared to the normal tissues. The proliferation of breast cancer cells was enhanced after DRD2 was upregulated and decreased after DRD2 was downregulated. In vivo experiments found that tumor growth and the expression of antigen KI-67 (Ki67) and the cluster of differentiation 31 (CD31) were improved by the overexpression of DRD2 and inhibited by the down expression of DRD2. In vivo and in vitro experiments demonstrated the phosphorylation of filamin A and extracellular signal-regulated kinase (FLNA-ERK) was influenced by the expression of DRD2, suggesting DRD2 plays a role in the FLNA-ERK signaling pathway. Methylation inhibitors (5-aza-2-deoxycytidine, 5-azadc) partially reversed the inhibitory effect of DRD2 down expression on cell proliferation, migration, and tumor growth in animal models, indicating that inhibition of DRD2 methylation promotes cancer development. This study demonstrated the DRD2 promoter region is hypomethylated in hormone-receptor-negative breast cancer or with high-risk factors. The methylation status of the DRD2 promoter and FLNA-ERK signaling pathway and the DRD2 expression in breast cancer treatment need to be considered. [ABSTRACT FROM AUTHOR]

Microcystic, elongated, and fragmented (MELF) pattern of invasion has seldom been documented in endocervical adenocarcinoma (EAC). The aim of this study was to analyze the clinicopathological characteristics of EAC showing MELF pattern. We collected the clinicopathological information of 10 cases of EAC with the MELF pattern and conducted polymer-based immunostaining for Ki-67 (dilution 1:200, clone MIB-1) on these cases. Ki-67 expression was assessed using the average estimation within the hotspot method. All tumors were human papillomavirus-associated EAC with Silva pattern C. All except one tumor exceeded 3 cm in size. Five tumors involved the entire thickness of the cervical stroma, and four tumors extended into the parametrium. Lymphovascular space invasion was identified in six cases. Two patients developed metastatic recurrences in the para-aortic lymph nodes and lungs, respectively. The MELF area showed significantly lower Ki-67 labelling index than that of a conventional tumor area. We confirmed our previous observation that the MELF area displayed lower proliferative activity than the conventional tumor area of EAC. We also demonstrated that patients with EAC showing MELF pattern had several adverse clinicopathological characteristics reflecting aggressive behavior. On the other hand, since the frequencies of post-operative recurrence and disease-related mortality that occurred during the follow-up period were relatively low, further investigations are warranted to clarify the prognostic value of MELF pattern in EAC patients. [ABSTRACT FROM AUTHOR]

Genetic and environmental factors are considered to play a significant role in the development of Urothelial Carcinoma (UC) of the urinary bladder, with various molecular markers being used for diagnostic and prognostic purposes. The aim of this study was to evaluate the expression of p53, Rb and Ki-67 in UC of the urinary bladder in our population group. Additionally, we investigated potential correlations in expression between p53 and Rb, as well as their associations with the Ki-67 proliferative index in urinary bladder UC. Tissue specimens of 70 samples of UC and 20 samples of non-tumorous bladder tissue were immunohistochemically stained with primary monoclonal antibodies against p53, Rb, and Ki-67 in our single-center study. When correlating expression levels of p53, Rb, and Ki-67 statistically significant higher expression for p53 and Ki-67 (p=0.001; p<0.001, respectively) was found with increasing grade and stage in UC of the bladder. Rb expression was decreased with increasing grade and stage but not statistically significant in our study group. Our study confirms the role of p53 and Rb alterations in UC of the urinary bladder. This is the first report of p53 and Rb alterations in UC of the urinary bladder in Kosovo population. [ABSTRACT FROM AUTHOR]

Objective: The value of DWI and 18F-FDG PET/CT in evaluating the expression of Ki-67 and GPC-3 in HCC was compared. Materials and methods: Ninety-four patients with primary HCC confirmed by pathology were retrospectively divided into high- and low-Ki-67-expression groups and positive- and negative-GPC-3 groups. The ADC and SUVmax values of the lesions in both groups were measured. ROC curves were used to evaluate the identification efficiency of parameters with significant differences for each group of lesions, and AUCwas calculated. The combined ADC and SUVmax values were analyzed by binary logistic regression. The Delong test was used to compare the AUC values of the combined and single parameters. Pearson (in line with normal distribution) or Spearman (in line with abnormal distribution) correlation analysis was used to analyze the correlation. Results: The ADC value of the high-Ki-67-expression group was lower than that of the low-Ki-67-expression group (P<0.05), and the SUVmax value of the highexpression group was higher than that of the low-expression group (P<0.05). The ADC value of the positive-GPC-3 group was lower than that of the negative group (P<0.0. tive group (P<0.05). The combined ADC and SUVmax values in the GPC-3 group were better than those of a single parameter (P<0.05). There was a strong negative correlation between the SUVmax value and ADC value in the Ki-67 group (R=-0.578, P<0.001) and a weak negative correlation between the SUVmax value and ADC value in the GPC-3 group (R=-0.279, P=0.006). The SUVmax value was strongly positively correlated with the Ki-67 expression index (R=0.733, P<0.001), while the ADC value was strongly negatively correlated with the Ki-67 expression index (R=-0.687, P<0.001). Conclusion: DWI and 18F-FDG PET/CT can be used to evaluate the expression of Ki-67 and GPC-3 in HCC, and there is a certain correlation between the ADC value and SUVmax. Combined DWI and 18F-FDG PET/CT is superior to a single technique in evaluating the expression of GPC-3 in HCC patients. However, the combined model did not benefit the Ki-67 group. [ABSTRACT FROM AUTHOR]

Objectives: Meningiomas are slow-growing brain neoplasms classified into three grades based on morphological criteria. While these grades are simple, they do not always correlate with patient outcomes. This study aimed to evaluate the status of estrogen receptor (ER), progesterone receptor (PR), and proliferation marker Ki-67/molecular immunology borstel-1 (MIB-1) in the three grades of meningioma. Methods: We evaluated the data of meningioma patients who were seen in our tertiary center over 10 years—8.5 years retrospectively and 1.5 years prospectively. Their archival hematoxylin and eosin stained slides were reviewed and re-graded according to the World Health Organization 2021 criteria. Immunohistochemical analysis for ER, PR, and Ki-67 was performed on all grade 2 and grade 3 meningiomas and 30 cases of grade 1 formalin-fixed, paraffin-embedded samples. Results: Of the 276 cases included in the study, there were 231 (83.7%) cases of grade 1 meningioma, 34 (12.3%) cases of grade 2, and 11 (4.0%) cases of grade 3. ER was positive in 26.0% of grade 1 tumors, 5.8% of grade 2, and 0.0% of grade 3. PR was positive in 70.0% of grade 1 tumors, 20.0% of grade 2, and 18.0% of grade 3. The Ki-67/MIB-1 labeling index (LI) was 2.1 in grade 1, 6.3 in grade 2, and 13.4 in grade 3 tumors. For both PR and Ki-67, the differences between grades 1, 2, and 3 tumors were significant (p < 0.001). There was a significant inverse relationship between mean Ki-67 LI and PR status, with increasing grade of tumor. Conclusions: Ki-67/MIB-1 LI has significant positive correlations with meningioma grade and its recurrence, which makes it a useful auxiliary method for the routine assessment of meningiomas, especially in patients with borderline atypia. The expression of PR, on the other hand, is a positive prognostic indicator and has a substantial correlation with histological grade. In cases of subtotal resection, high proliferative/recurrence rates, and borderline histopathology, the PR status in combination with the MIB-1 LI can offer insights into the behavior and the recurrence probability of a meningioma.

Objectives: Ameloblastoma, comprising approximately 11% of all odontogenic tumors, is a locally aggressive tumor with a high recurrence rate. This study aimed to assess the immunohistochemical expression of Ki-67 and p53 and their association with clinical and pathological factors among patients with ameloblastoma. Methods: Retrospective follow-up data of patients histologically confirmed with ameloblastoma at Makerere College of Health Sciences in Kampala, Uganda from January 2012 to December 2018 were retrieved. Factors associated with Ki-67 and p53 immunohistochemical expression were determined using one-way one-way analysis of variance. Chi-square and Fisher’s exact statistical tests were used to assess factors associated with recurrence. A two-tailed p < 0.05 was considered statistically significant. Results: A total of 40 patients confirmed histologically with ameloblastoma were included in the analysis. The majority (62.5%) of cases were of the conventional type of ameloblastoma. The expressions of Ki-67 and p53 were 52.5% and 85.0%, respectively. Recurrence was found in 47.5% of patients and it was associated with conventional histological type (p=0.042), segmental resection (p < 0.001), tumor size (p < 0.001), and high p53 expression (p=0.041). Conclusions: Almost half the cases in this study had recurrence. The immunohistochemical expression of p53 was significantly higher than that of Ki-67.

Tubo-ovarian high-grade serous carcinomas (HGSC) are highly proliferative neoplasms that generally respond well to platinum/taxane chemotherapy. We recently identified minichromosome maintenance complex component 3 (MCM3), which is involved in the initiation of DNA replication and proliferation, as a favorable prognostic marker in HGSC. Our objective was to further validate whether MCM3 mRNA expression and possibly MCM3 protein levels are associated with survival in patients with HGSC. MCM3 mRNA expression was measured using NanoString expression profiling on formalin-fixed and paraffin-embedded tissue (N = 2355 HGSC) and MCM3 protein expression was assessed by immunohistochemistry (N = 522 HGSC) and compared with Ki-67. Kaplan-Meier curves and the Cox proportional hazards model were used to estimate associations with survival. Among chemotherapy-naïve HGSC, higher MCM3 mRNA expression (one standard deviation increase in the score) was associated with longer overall survival (HR = 0.87, 95% CI 0.81-0.92, p

Neurodevelopmental cognitive disorders provide insights into mechanisms of human brain development. Here, we report an intellectual disability syndrome caused by the loss of APC7, a core component of the E3 ubiquitin ligase anaphase promoting complex (APC). In mechanistic studies, we uncover a critical role for APC7 during the recruitment and ubiquitination of APC substrates. In proteomics analyses of the brain from mice harboring the patient-specific APC7 mutation, we identify the chromatin-associated protein Ki-67 as an APC7-dependent substrate of the APC in neurons. Conditional knockout of the APC coactivator protein Cdh1, but not Cdc20, leads to the accumulation of Ki-67 protein in neurons in vivo, suggesting that APC7 is required for the function of Cdh1-APC in the brain. Deregulated neuronal Ki-67 upon APC7 loss localizes predominantly to constitutive heterochromatin. Our findings define an essential function for APC7 and Cdh1-APC in neuronal heterochromatin regulation, with implications for understanding human brain development and disease.

BackgroundT cell activation (HLA-DR, CD-38), proliferation (KI-67), and functional (IFN-γ, TNF-α) markers have recently been shown to be useful in predicting and monitoring anti-TB responses in smear positive TB, but previous research did not characterize the activation and proliferation profiles after therapy of smear negative TB.MethodologyIn this study, we used polychromatic flow cytometry to assess selected PPD-specific T cell markers using fresh PBMC of smear negative and positive pulmonary tuberculosis (PTB) patients, recruited from health facilities in Addis Ababa.ResultLevels of activation (HLA-DR, CD38) and proliferation (Ki-67) among total unstimulated CD4 T cells decreased significantly after therapy, particularly at month 6. Similarly, levels of PPD-specific T cell activation markers (HLA-DR, CD-38) were significantly lower in smear positive PTB patients following treatment, whereas a consistent decline in these markers was less apparent among smear negative PTB patients at the sixth month.ConclusionAfter six months of standard anti-TB therapy, persistent levels of activation of HLA-DR and CD-38 from PPD specific CD4+T cells in this study could indicate that those markers have little value in monitoring and predicting anti-TB treatment response in smear negative pulmonary TB patients in Ethiopian context.

Multiplexed mRNA profiling in the spatial context provides new information enabling basic research and clinical applications. Unfortunately, existing spatial transcriptomics methods are limited due to either low multiplexing or complexity. Here, we introduce a spatialomics technology, termed Multi Omic Single-scan Assay with Integrated Combinatorial Analysis (MOSAICA), that integrates in situ labeling of mRNA and protein markers in cells or tissues with combinatorial fluorescence spectral and lifetime encoded probes, spectral and time-resolved fluorescence imaging, and machine learning-based decoding. We demonstrate MOSAICA's multiplexing scalability in detecting 10-plex targets in fixed colorectal cancer cells using combinatorial labeling of five fluorophores with facile error-detection and removal of autofluorescence. MOSAICA's analysis is strongly correlated with sequencing data (Pearson's r = 0.96) and was further benchmarked using RNAscopeTM and LGC StellarisTM. We further apply MOSAICA for multiplexed analysis of clinical melanoma Formalin-Fixed Paraffin-Embedded (FFPE) tissues. We finally demonstrate simultaneous co-detection of protein and mRNA in cancer cells.

Introduction: The identification of bladder detrusor muscle invasion in urothelial cancer is essential for prognosis and management. We studied the clinical, histological, and immunohistochemical expression of p16, p53, and Ki-67 in urothelial detrusor muscle-invasive bladder cancer (MIBC) and urothelial non-detrusor muscle-invasive bladder cancer (NMIBC) in Egyptian patients. Methods: Sixty-two bladder urothelial cancer cases obtained through TURBT were included and divided into two groups: (MIBC, stage T2) and NMIBC (T1). Tissue blocks were recut and re-examined microscopically; then, the immunostaining of p16, p53, and Ki-67 was performed to compare both groups and evaluate the 13% cut-off for Ki-67, 20% for p53, and p16 intensity in various conditions aided by telepathology technology. Results and conclusion: Hematuria was the main clinical first presentation, with no significant difference between either group. The mean age was 61.6 years, with male predominance (52 males and 10 females). The absence of papillary histological pattern was associated with a higher stage, including detrusor muscle invasion (p = 0.000). The overall average percent of p53 immunostaining was 12.9%, revealing no significant difference between MIBC and NMIBC when a cut-off of 20% was implicated. The Ki-67 expression was correlated with higher grade and muscle invasion; however, no association was found with the other two markers’ expression. The negative immunostaining of p16 was associated with low grade and NMIBC in the case of the preservation of the papillary pattern. We recommend further studies on the cut-off of widely used markers and more immunohistochemical and genetic studies on the p16(INK4A), taking into consideration the histological pattern of conventional carcinomas.

Focal reactive nodular gliosis (FRNG) is an extremely rare benign retinal reactive astrocytic tumor that results from the proliferation of well-diferentiated glial cells secondary to a variety of retinal conditions. We describe a case of this tumor in a 64-year-old male in association with a chorioretinal scar he has had since childhood. The symptom was sudden painful vision loss. In the clinical examination, iris rubeosis, posterior synechiae, cataract, vitreous haze and a suspected fundus mass were showed. B-scan ultrasonography demonstrated a retinal mass consistent with choroidal melanoma. The magnetic resonance imaging (MRI) showed a well-circumscribed mass with T1 hyperintensity and T2 hypointensity. Enucleation was performed and histopathologic and immunohistochemical studies confirmed the diagnosis of FRNG.

Background: To explore the value of multiparametric MRI markers for preoperative prediction of Ki-67 expression among patients with rectal cancer. Methods: Data from 259 patients with postoperative pathological confirmation of rectal adenocarcinoma who had received enhanced MRI and Ki-67 detection was divided into 4 cohorts: training (139 cases), internal validation (in-valid, 60 cases), and external validation (ex-valid, 60 cases) cohorts. The patients were divided into low and high Ki-67 expression groups. In the training cohort, DWI, T2WI, and contrast enhancement T1WI (CE-T1) sequence radiomics features were extracted from MRI images. Radiomics marker scores and regression coefficient were then calculated for data fitting to construct a radscore model. Subsequently, clinical features with statistical significance were selected to construct a combined model for preoperative individualized prediction of rectal cancer Ki-67 expression. The models were internally and externally validated, and the AUC of each model was calculated. Calibration and decision curves were used to evaluate the clinical practicality of nomograms. Results: Three models for predicting rectal cancer Ki-67 expression were constructed. The AUC and Delong test results revealed that the combined model had better prediction performance than other models in three chohrts. A decision curve analysis revealed that the nomogram based on the combined model had relatively good clinical performance, which can be an intuitive prediction tool for clinicians. Conclusion: The multiparametric MRI radiomics model can provide a noninvasive and accurate auxiliary tool for preoperative evaluation of Ki-67 expression in patients with rectal cancer and can support clinical decision-making. [ABSTRACT FROM AUTHOR]

Integrating carrier drug therapy with recent advances in liver tissue regeneration, this paper proposes a novel nanomedicine-based approach to drug delivery, with the aim of enhancing the regenerative capacity of hepatocytes and improving liver function after partial hepatectomy. The proposed decellularized liver matrix provides excellent biocompatibility and similarity to natural liver components, while the molecules encapsulated in the carrier (tannic acid) promote liver regeneration. In in vitro cultures, the 0.001 mg/mL TA-mPEG-DLM group consistently outperformed the blank group in terms of albumin synthesis: Day 1 (11.1 ± 2.4 vs. 8.2 ± 0.7), Day 3 (5.8 ± 1.3 vs. 4.2 ± 0.4), and Day 5 (1.6 ± 0.3 vs. 1.2 ± 0.2) (μg/100% proliferation rate/well/day). In a liver-injured in vivo model, the 0.5 mg/mL TA-mPEG-DLM group outperformed the blank group in terms of relative liver weight: Day 3 (3.50 ± 0.09% vs. 3.22 ± 0.03%) and Day 7 (4.13 ± 0.21% vs. 3.72 ± 0.06%). Furthermore, the TA-mPEG-DLM group outperformed the blank group in terms of Ki-67 expression in hepatocytes on Day 7 (192.7 ± 34.1% vs. 150.4 ± 11.6%). Taken together, these findings indicate that the proposed drug delivery strategy is a promising approach to liver regeneration following partial hepatectomy with potential for clinical translation. [ABSTRACT FROM AUTHOR]

Our study aims to reveal clinically helpful prognostic markers using quantitative radiologic data from perfusion magnetic resonance imaging for patients with locally advanced carcinoma, using the Ki-67 index as a surrogate. Patients who received a breast cancer diagnosis and had undergone dynamic contrast-enhanced magnetic resonance imaging of the breast for pretreatment evaluation and follow-up were searched retrospectively. We evaluated the MRI studies for perfusion parameters and various categories and compared them to the Ki-67 index. Axillary involvement was categorized as low (N0–N1) or high (N2–N3) according to clinical stage. A total sum of 60 patients' data was included in this study. Perfusion parameters and Ki-67 showed a significant correlation with the transfer constant (Ktrans) (ρ = 0.554 p = 0.00), reverse transfer constant (Kep) (ρ = 0.454 p = 0.00), and initial area under the gadolinium curve (IAUGC) (ρ = 0.619 p = 0.00). The IAUGC was also significantly different between axillary stage groups (Z = 2.478 p = 0.013). Outside of our primary hypothesis, associations between axillary stage and contrast enhancement (x2 = 8.023 p = 0.046) and filling patterns (x2 = 8.751 p = 0.013) were detected. In conclusion, these parameters are potential prognostic markers in patients with moderate Ki-67 indices, such as those in our study group. The relationship between axillary status and perfusion parameters also has the potential to determine patients who would benefit from limited axillary dissection. [ABSTRACT FROM AUTHOR]

Direct DNA double-strand breaks result in phosphorylation of H2AX, a variant of the histone H2 protein. Phosphorylated H2AX (γH2AX) may be a potential indicator in the evaluation of genotoxicity and hepatocarcinogenicity. In this study, γH2AX and Ki-67 were detected in the short-term responses (24 h after chemical administration) to classify genotoxic hepatocarcinogens (GHs) from non-GH chemicals. One hundred and thirty-five 6-week-old Crl: CD(SD) (SPF) male rats were treated with 22 chemicals including 11 GH and 11 non-GH, sacrificed 24 h later, and immunostained with γH2AX and Ki-67. Positivity rates of these markers were measured in the 3 liver ZONEs 1–3; portal, lobular, and central venous regions. These values were input into 3 machine learning models—Naïve Bayes, Random Forest, and k-Nearest Neighbor to classify GH and non-GH using a 10-fold cross-validation method. All 11 and 10 out of 11 GH caused significant increase in γH2AX and Ki-67 levels, respectively (P  < .05). Of the 3 machine learning models, Random Forest performed the best. GH were identified with 95.0% sensitivity (76/80 GH-treated rats), 90.9% specificity (50/55 non-GH-treated rats), and 90.0% overall correct response rate using γH2AX staining, and 96.2% sensitivity (77/80), 81.8% specificity (45/55), and 90.4% overall correct response rate using Ki-67 labeling. Random Forest model using γH2AX and Ki-67 could independently predict GH in the early stage with high accuracy. [ABSTRACT FROM AUTHOR]

Extraction of impacted and dystopic third molars is a rather traumatic manipulation accompanied by a large bone defect and wound infection. Therefore, it is advisable to perform hermectomy, which has a number of advantages over typical and atypical methods of tooth extraction. An important stage of any surgical intervention is the postoperative period, which is characterized by a certain duration and the presence of complications, which is due, among other things, to the regenerative potential of tissues, especially epithelial tissues. Aim of the study is to evaluate the condition of the gingival epithelium in the area of third molars in children who have to have these teeth extracted for orthodontic reasons, taking into account the stage of tooth formation, i. e. its root. Material and Methods. Third molar extraction for orthodontic indications was performed in 95 children aged 11 to 18 years. Clinical and radiologic examinations were performed in three groups: Group I (n=30) - children aged 11-13 years; Group II (n=35) - children aged 13-16 years, and Group III (n=30) - children aged 16-18 years. During surgery, gingival tissue was taken from the adjacent areas for examination. The material was fixed, dehydrated, and paraffin-embedded for histologic processing. Immunohistochemical techniques were performed according to the manufacturer's protocols. Specifically, immunohistochemical detection of Ki-67 antigen was performed with primary antibodies against it. Digital copies of the images were analyzed using the specialized computer program ImageJ v1.52 (freeware, USA). The obtained digital data were statistically processed. The digital data obtained were statistically processed. A preliminary test for normality of the distribution was carried out using the Shapiro-Wilks method. According to this criterion, the hypothesis of normality of the distribution was not rejected for all the statistical samples studied (at the significance level of p=0.05), so we used mainly parametric methods of statistical analysis: calculation of the arithmetic mean and its error, unpaired two-sided Student's t-test. However, because the statistical samples were small, the non-parametric Mann-Whitney test was used in addition to the Student's t-test. The study was conducted as part of the complex research work of the Department of Pediatric Dentistry of the Bukovinian State Medical University on the topic «Development of methods of prevention and treatment of the main dental diseases in children, taking into account the risk factors of their development» (state registration number: 0121U110122). The conducted research complied with bioethical norms, as stated in the conclusions of the Bioethics Commission of the Bukovinian State Medical University (№ 1 dated 17.09.2020). Conclusions. Thus, the histological and immunohistochemical study of the gingiva in the area of the third molar allows us to conclude that during the formation of the root of this tooth, a number of changes occur in the epithelial cover of the gingiva, namely: an increase in the number of epithelial layers with a decrease in their proliferative activity. The obtained data indicate a decrease in the regenerative potential of the multilayered squamous epithelium with increasing age of the child and the degree of third molar formation, which is reflected in the clinical picture of the course of surgical intervention. [ABSTRACT FROM AUTHOR]

Background: Immunohistochemistry‐based protein biomarkers can provide useful prognostic information in cutaneous melanoma. The independent prognostic value of Ki‐67 has been studied with variable results. PReferentially expressed Antigen in MElanoma (PRAME) immunohistochemistry is a useful new ancillary tool for distinguishing cutaneous nevi from melanoma; however, its prognostic value has not been well studied. We evaluated PRAME as a prognostic marker in cutaneous melanoma, compared to Ki‐67. Methods: We analyzed the immunohistochemical expression of PRAME and Ki‐67 in 165 melanocytic lesions, including 92 primary melanomas, 19 metastatic melanomas, and 54 melanocytic nevi using tissue microarrays. PRAME immunostaining was scored based on the percentage of positive nuclei: 0 <1%, 1+ 1%–25%, 2+ 26%–50%, 3+ 51%–75%, and 4+ >75%. The percentage of Ki‐67‐positive tumor nuclei was used to calculate the proliferation index. Results: PRAME and Ki‐67 both showed significantly increased expression in melanomas compared to nevi (p < 0.0001 and p < 0.001, respectively). There was no significant difference in PRAME expression in primary versus metastatic melanomas. By contrast, the Ki‐67 proliferation index was higher in metastatic melanoma than in primary melanoma (p = 0.013). Increased Ki‐67 index correlated with ulceration (p < 0.001), increased Breslow depth (p = 0.001), and higher mitotic rate (p < 0.0001), whereas increased PRAME expression correlated with higher mitotic rate (p = 0.047) and Ki‐67 index (p = 0.007). Increased Ki‐67 index correlated with worse disease‐specific survival in patients with primary melanoma (p < 0.001), but PRAME expression did not show prognostic significance in disease‐specific survival (p = 0.63). In a multivariable analysis of patients with primary melanoma, tumor Breslow depth, ulceration, mitotic rate, and Ki‐67 index were each independent predictors of disease‐specific survival (p = 0.006, 0.02, 0.001, and 0.04, respectively); however, PRAME expression was not predictive of disease‐specific survival (p = 0.64). Conclusion: Ki‐67 is an independent prognostic marker; although increased PRAME expression correlates with the Ki‐67 proliferation index and mitotic rate, PRAME is not an independent prognostic marker for cutaneous melanoma. PRAME and Ki‐67 are useful ancillary tools for distinguishing benign from malignant melanocytic lesions. [ABSTRACT FROM AUTHOR]

Introduction: Breast cancer is the most common cancer in women; its early detection plays a crucial role in improving patient outcomes. Ki-67 is a biomarker commonly used for evaluating the proliferation of cancer cells in breast cancer patients. The quantification of Ki-67 has traditionally been performed by pathologists through a manual examination of tissue samples, which can be time-consuming and subject to inter- and intra-observer variability. In this study, we used a novel deep learning model to quantify Ki-67 in breast cancer in digital images prepared by a microscope-attached camera. Objective: To compare the automated detection of Ki-67 with the manual eyeball/hotspot method. Place and duration of study: This descriptive, cross-sectional study was conducted at the Jinnah Sindh Medical University. Glass slides of diagnosed cases of breast cancer were obtained from the Aga Khan University Hospital after receiving ethical approval. The duration of the study was one month. Methodology: We prepared 140 digital images stained with the Ki-67 antibody using a microscope-attached camera at 10×. An expert pathologist (P1) evaluated the Ki-67 index of the hotspot fields using the eyeball method. The images were uploaded to the DeepLiif software to detect the exact percentage of Ki-67 positive cells. SPSS version 24 was used for data analysis. Diagnostic accuracy was also calculated by other pathologists (P2, P3) and by AI using a Ki-67 cut-off score of 20 and taking P1 as the gold standard. Results: The manual and automated scoring methods showed a strong positive correlation as the kappa coefficient was significant. The p value was <0.001. The highest diagnostic accuracy, i.e., 95%, taking P1 as gold standard, was found for AI, compared to pathologists P2 and P3. Conclusions: Use of quantification-based deep learning models can make the work of pathologists easier and more reproducible. Our study is one of the earliest studies in this field. More studies with larger sample sizes are needed in future to develop a cohort. [ABSTRACT FROM AUTHOR]

Objective: Noninvasive detection of molecular status of astrocytoma is of great clinical significance for predicting therapeutic response and prognosis. We aimed to evaluate whether morphological MRI (mMRI), SWI, DWI, and DSC-PWI could predict Ki-67 labeling index (LI), ATRX mutation, and MGMT promoter methylation status in IDH mutant (IDH-mut) astrocytoma. Methods: We retrospectively analyzed mMRI, SWI, DWI, and DSC-PWI in 136 patients with IDH-mut astrocytoma.The features of mMRI and intratumoral susceptibility signals (ITSS) were compared using Fisher exact test or chi-square tests. Wilcoxon rank sum test was used to compare the minimum ADC (ADCmin), and minimum relative ADC (rADCmin) of IDH-mut astrocytoma in different molecular markers status. Mann–Whitney U test was used to compare the rCBVmax of IDH-mut astrocytoma with different molecular markers status. Receiver operating characteristic curves was performed to evaluate their diagnostic performances. Results: ITSS, ADCmin, rADCmin, and rCBVmax were significantly different between high and low Ki-67 LI groups. ITSS, ADCmin, and rADCmin were significantly different between ATRX mutant and wild-type groups. Necrosis, edema, enhancement, and margin pattern were significantly different between low and high Ki-67 LI groups. Peritumoral edema was significantly different between ATRX mutant and wild-type groups. Grade 3 IDH-mut astrocytoma with unmethylated MGMT promoter was more likely to show enhancement compared to the methylated group. Conclusions: mMRI, SWI, DWI, and DSC-PWI were shown to have the potential to predict Ki-67 LI and ATRX mutation status in IDH-mut astrocytoma. A combination of mMRI and SWI may improve diagnostic performance for predicting Ki-67 LI and ATRX mutation status. Clinical relevance statement: Conventional MRI and functional MRI (SWI, DWI, and DSC-PWI) can predict Ki-67 expression and ATRX mutation status of IDH mutant astrocytoma, which may help clinicians determine personalized treatment plans and predict patient outcomes. Key Points: • A combination of multimodal MRI may improve the diagnostic performance to predict Ki-67 LI and ATRX mutation status. • Compared with IDH-mutant astrocytoma with low Ki-67 LI, IDH-mutant astrocytoma with high Ki-67 LI was more likely to show necrosis, edema, enhancement, poorly defined margin, higher ITSS levels, lower ADC, and higher rCBV. • ATRX wild-type IDH-mutant astrocytoma was more likely to show edema, higher ITSS levels, and lower ADC compared to ATRX mutant IDH-mutant astrocytoma. [ABSTRACT FROM AUTHOR]

Canine soft tissue sarcoma (STS) is relatively common in dogs and is the generic term for tumours that originate from mesenchymal cells. While histopathological grade and immunolabelling with Ki-67 have been used for estimating prognosis, additional indicators are needed for predicting prognosis. Aberrant cell signalling pathways may contribute to disease activity and, therefore, prognostic markers. However, their role in canine STS remains poorly understood. The aim of this study was to investigate expression of phosphorylated Akt (phospho-Akt) and phosphorylated S6 (phospho-S6) as potential prognostic indicators. Immunohistochemical labelling was conducted on clinical samples of canine STS (n = 67). We found that phospho-Akt expression was positively correlated with histopathological grade (P = 0.001) and Ki-67 index (P <0.01). There was no apparent relationship between the type of STS and the expression of phospho-Akt. The number of cases that expressed phospho-S6, which is the downstream molecule of the Akt signalling pathway, was higher in immunopositive phospho-Akt cases than in immunonegative phospho-Akt cases (P <0.0001). Furthermore, phospho-Akt expression was significantly higher in recurrent and metastatic cases. We also confirmed that phosphorylation of Akt occurred in conjunction with S6 phosphorylation in three canine STS cell lines. These results suggest that immunolabelling for phospho-Akt, phospho-S6 and Ki-67 could potentially be used as a prognostic indicator and therapeutic target in canine STS. [ABSTRACT FROM AUTHOR]

Background and Aim: USP22 is a positive regulator in tumor growth, its depletion leads to cell cycle arrest at G1 phase. USP22 over expression was positively correlated with proteins involved in proliferation and negatively correlated with tumor suppressor protein tumor supprn. Ki-67 expression is associated with USP22 over expression in oral squamous cell carcinoma (OSCC) and also in cervical and prostate cancers. The aim of this study is to evaluate the expression of USP22 and Ki-67 in OSCC by using an immunohistochemical staining procedure. Materials and Methods: Immunohistochemistry was used to determine the expression of USP22 protein in 50 archival tissue blocks of histopathologically diagnosed OSCC and 15 normal oral mucosa tissue blocks. The histopathological correlation of USP22 with Ki-67 was done. Results: Expression of USP22 and Ki-67 was seen in the nuclei of epithelial cells. Statistical analysis of the mean expression of USP22 in OSCC and normal tissue showed a significant difference (P = 0.000000119). A significant difference was also observed in Ki-67 between OSCC and normal tissue (P = 0.00000086). Correlation test showed a weak correlation (R = 0.19) between USP22 and Ki-67 expression of group 1. Similarly, a weak correlation (R = 0.51) was observed in group 2. Conclusion: A statistically significant difference in the expression of USP22 and Ki-67 was observed between normal mucosa and OSCC. It can be used in early diagnosis of OSCC but its use as a prognostic indicator is questionable and should be exemplified with a larger study sample. [ABSTRACT FROM AUTHOR]

Background: The WHO grade and Ki-67 index are independent indices used to evaluate the malignant biological behavior of meningioma. This study aims to develop MRI-based machine learning models to predict the malignant biological behavior of meningioma from the perspective of the WHO grade, Ki-67 index, and their combination. Methods: This multicenter, retrospective study included 313 meningioma patients, of which 70 were classified as high-grade (WHO II/III) and 243 as low-grade (WHO I). The Ki-67 expression was classified into low-expression (n = 216) and high-expression (n = 97) groups with a threshold of 5%. Among them, there were 128 patients with malignant biological behavior whose WHO grade or Ki-67 index increased either or both. Data from Center A and B are were utilized for model development, while data from Center C and D were used for external validation. Radiomic features were extracted from the maximum cross-sectional area (2D) region of Interest (ROI) and the whole tumor volume (3D) ROI using different paraments from the T1, T2-weighted, and T1 contrast-enhanced sequences (T1CE), followed by five independent feature selections and eight classifiers. 240 prediction models were constructed to predict the WHO grade, Ki-67 index and their combination respectively. Models were evaluated by cross-validation in training set (n = 224). Suitable models were chosen by comparing the cross-validation (CV) area under the curves (AUC) and their relative standard deviations (RSD). Clinical and radiological features were collected and analyzed; meaningful features were combined with radiomic features to establish the clinical-radiological-radiomic (CRR) models. The receiver operating characteristic (ROC) analysis was used to evaluate those models in validation set. Radiomic models and CRR models were compared by Delong test. Results: 1218 and 1781 radiomic features were extracted from 2D ROI and 3D ROI of each sequence. The selected grade, Ki-67 index and their combination radiomic models were T1CE-2D-LASSO-LR, T1CE-3D-LASSO-NB, and T1CE-2D-LASSO-LR, with cross-validated AUCs on the training set were 0.857, 0.798, and 0.888, the RSDs were 0.06, 0.09, and 0.05, the validation set AUCs were 0.829, 0.752, and 0.904, respectively. Heterogeneous enhancement was found to be associated with high grade and Ki-67 status, while surrounding invasion was associated with the high grade status, peritumoral edema and cerebrospinal fluid space surrounding tumor were correlated with the high Ki-67 status. The Delong test showed that these significant radiological features did not significantly improve the predictive performance. The AUCs for CRR models predicting grade, Ki-67 index, and their combination in the validation set were 0.821, 0.753, and 0.906, respectively. Conclusions: This study demonstrated that MRI-based machine learning models could effectively predict the grade, Ki-67 index of meningioma. Models considering these two indices might be valuable for improving the predictive sensitivity and comprehensiveness of prediction of malignant biological behavior of meningioma. [ABSTRACT FROM AUTHOR]

Background: This study aimed to develop a computed tomography (CT) model to predict Ki-67 expression in hepatocellular carcinoma (HCC) and to examine the added value of radiomics to clinico-radiological features. Methods: A total of 208 patients (training set, n = 120; internal test set, n = 51; external validation set, n = 37) with pathologically confirmed HCC who underwent contrast-enhanced CT (CE-CT) within 1 month before surgery were retrospectively included from January 2014 to September 2021. Radiomics features were extracted and selected from three phases of CE-CT images, least absolute shrinkage and selection operator regression (LASSO) was used to select features, and the rad-score was calculated. CE-CT imaging and clinical features were selected using univariate and multivariate analyses, respectively. Three prediction models, including clinic-radiologic (CR) model, rad-score (R) model, and clinic-radiologic-radiomic (CRR) model, were developed and validated using logistic regression analysis. The performance of different models for predicting Ki-67 expression was evaluated using the area under the receiver operating characteristic curve (AUROC) and decision curve analysis (DCA). Results: HCCs with high Ki-67 expression were more likely to have high serum α-fetoprotein levels (P = 0.041, odds ratio [OR] 2.54, 95% confidence interval [CI]: 1.04–6.21), non-rim arterial phase hyperenhancement (P = 0.001, OR 15.13, 95% CI 2.87–79.76), portal vein tumor thrombus (P = 0.035, OR 3.19, 95% CI: 1.08–9.37), and two-trait predictor of venous invasion (P = 0.026, OR 14.04, 95% CI: 1.39–144.32). The CR model achieved relatively good and stable performance compared with the R model (AUC, 0.805 [95% CI: 0.683–0.926] vs. 0.678 [95% CI: 0.536–0.839], P = 0.211; and 0.805 [95% CI: 0.657–0.953] vs. 0.667 [95% CI: 0.495–0.839], P = 0.135) in the internal and external validation sets. After combining the CR model with the R model, the AUC of the CRR model increased to 0.903 (95% CI: 0.849–0.956) in the training set, which was significantly higher than that of the CR model (P = 0.0148). However, no significant differences were found between the CRR and CR models in the internal and external validation sets (P = 0.264 and P = 0.084, respectively). Conclusions: Preoperative models based on clinical and CE-CT imaging features can be used to predict HCC with high Ki-67 expression accurately. However, radiomics cannot provide added value. [ABSTRACT FROM AUTHOR]

Simple Summary: This review aims to shed light on the proliferative markers important in the everyday clinical management of colorectal cancer (CRC), ranging from simple methods of assessing cellular proliferation (e.g., DNA ploidy, BrdUrd/IdUrd/tritiated thymidine binding index) to the use of immunohistochemistry (IHC) and modern molecular biology techniques (e.g., qRT-PCR, in situ hybridization, RNA/DNA sequencing) for the detection of genetic and epigenetic markers. Among the examined markers, the prognostic utility was demonstrated for aneuploidy and the overexpression of IHC markers (e.g., TS, cyclin B1, and D1, PCNA, and Ki-67). Classical genetic markers of prognostic significance mostly comprise mutations in commonly examined genes such as APC, KRAS/BRAF, TGF-β, and TP53. Chromosomal markers include CIN and MSI, while CIMP is indicated as a potential epigenetic marker with many other candidates such as SERP, p14, p16, LINE-1, and RASSF1A. Modern technology-based approaches to study non-coding fragments of the human genome have also yielded some candidates for CRC prognostic markers among the lncRNAs (e.g., SNHG1, SNHG6, MALAT-1, CRNDE) and miRNAs (e.g., miR-20a, miR-21, miR-143, miR-145, miR-181a/b). With growing knowledge of the human genome structure and the rapid development of molecular biology techniques, it is hoped that a panel of reliable prognostic markers could improve the assessment of survival as well as allow for the better estimation of the treatment outcomes for CRC patients. Colorectal cancer (CRC) is one of the most common and severe malignancies worldwide. Recent advances in diagnostic methods allow for more accurate identification and detection of several molecular biomarkers associated with this cancer. Nonetheless, non-invasive and effective prognostic and predictive testing in CRC patients remains challenging. Classical prognostic genetic markers comprise mutations in several genes (e.g., APC, KRAS/BRAF, TGF-β, and TP53). Furthermore, CIN and MSI serve as chromosomal markers, while epigenetic markers include CIMP and many other candidates such as SERP, p14, p16, LINE-1, and RASSF1A. The number of proliferation-related long non-coding RNAs (e.g., SNHG1, SNHG6, MALAT-1, CRNDE) and microRNAs (e.g., miR-20a, miR-21, miR-143, miR-145, miR-181a/b) that could serve as potential CRC markers has also steadily increased in recent years. Among the immunohistochemical (IHC) proliferative markers, the prognostic value regarding the patients' overall survival (OS) or disease-free survival (DFS) has been confirmed for thymidylate synthase (TS), cyclin B1, cyclin D1, proliferating cell nuclear antigen (PCNA), and Ki-67. In most cases, the overexpression of these markers in tissues was related to worse OS and DFS. However, slowly proliferating cells should also be considered in CRC therapy (especially radiotherapy) as they could represent a reservoir from which cells are recruited to replenish the rapidly proliferating population in response to cell-damaging factors. Considering the above, the aim of this article is to review the most common proliferative markers assessed using various methods including IHC and selected molecular biology techniques (e.g., qRT-PCR, in situ hybridization, RNA/DNA sequencing, next-generation sequencing) as prognostic and predictive markers in CRC. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular cancer (HCC) is one of the most common tumors worldwide, and Ki-67 is highly important in the assessment of HCC. Our study aimed to evaluate the value of ultrasound radiomics based on intratumoral and peritumoral tissues in predicting Ki-67 expression levels in patients with HCC. Methods: We conducted a retrospective analysis of ultrasonic and clinical data from 118 patients diagnosed with HCC through histopathological examination of surgical specimens in our hospital between September 2019 and January 2023. Radiomics features were extracted from ultrasound images of both intratumoral and peritumoral regions. To select the optimal features, we utilized the t-test and the least absolute shrinkage and selection operator (LASSO). We compared the area under the curve (AUC) values to determine the most effective modeling method. Subsequently, we developed four models: the intratumoral model, the peritumoral model, combined model #1, and combined model #2. Results: Of the 118 patients, 64 were confirmed to have high Ki-67 expression while 54 were confirmed to have low Ki-67 expression. The AUC of the intratumoral model was 0.796 (0.649-0.942), and the AUC of the peritumoral model was 0.772 (0.619-0.926). Furthermore, combined model#1 yielded an AUC of 0.870 (0.751-0.989), and the AUC of combined model#2 was 0.762 (0.605-0.918). Among thesemodels, combinedmodel#1 showed the best performance in terms of AUC, accuracy, F1-score, and decision curve analysis (DCA). Conclusion: We presented an ultrasound radiomics model that utilizes both intratumoral and peritumoral tissue information to accurately predict Ki-67 expression in HCC patients. We believe that incorporating both regions in a proper manner can enhance the diagnostic performance of the prediction model. Nevertheless, it is not sufficient to include both regions in the region of interest (ROI) without careful consideration. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to explore the efficacy of the computed tomography (CT) radiomics model for predicting the Ki-67 proliferation index (PI) of pure-solid non-small cell lung cancer (NSCLC). Materials and methods: This retrospective study included pure-solid NSCLC patients from five centers. The radiomics features were extracted from thin-slice, non-enhanced CT images of the chest. The minimum redundancy maximum relevance (mRMR) and least absolute shrinkage and selection operator (LASSO) were used to reduce and select radiomics features. Logistic regression analysis was employed to build predictive models to determine Ki-67-high and Ki-67-low expression levels. Three prediction models were established: the clinical model, the radiomics model, and the nomogram model combining the radiomics signature and clinical features. The prediction efficiency of different models was evaluated using the area under the curve (AUC). Results: A total of 211 NSCLC patients with pure-solid nodules or masses were included in the study (N=117 for the training cohort, N=49 for the internal validation cohort, and N=45 for the external validation cohort). The AUC values for the clinical models in the training, internal validation, and external validation cohorts were 0.73 (95% CI: 0.64-0.82), 0.75 (95% CI:0.62-0.89), and 0.72 (95% CI: 0.57-0.86), respectively. The radiomics models showed good predictive ability in diagnosing Ki-67 expression levels in the training cohort (AUC, 0.81 [95% CI: 0.73-0.89]), internal validation cohort (AUC, 0.81 [95% CI: 0.69-0.93]) and external validation cohort (AUC, 0.78 [95% CI: 0.64-0.91]). Compared to the clinical and radiomics models, the nomogram combining both radiomics signatures and clinical features had relatively better diagnostic performance in all three cohorts, with the AUC of 0.83 (95% CI: 0.76-0.90), 0.83 (95% CI: 0.71-0.94), and 0.81 (95% CI: 0.68-0.93), respectively. Conclusion: The nomogram combining the radiomics signature and clinical features may be a potential non-invasive method for predicting Ki-67 expression levels in patients with pure-solid NSCLC. [ABSTRACT FROM AUTHOR]

Background: Ki‐67 is an index of proliferative activity and is an established predictive and prognostic marker in multiple malignancies. However, its prognostic relevance in multiple myeloma (MM) is unclear. We investigated the relationship between Ki‐67 expression and survival outcomes in MM in the era of novel therapies. Methods: We interrogated our database to identify patients with MM, newly diagnosed between July 1, 2013 and December 31, 2020, with Ki‐67 expression assessed by immunohistochemistry (IHC) on bone marrow biopsies. Using an established threshold of 5% we defined Ki‐67low (≤5%) and Ki‐67high (>5%) subgroups for association with progression‐free survival (PFS) and overall survival (OS). Results: Of 167 patients included: 53 (31.7%) had Ki‐67high and 114 had Ki‐67low. More patients with R‐ISS 3 had Ki‐67high (22.2% vs. 9.7%). The gain of 1q21 was overrepresented in the Ki‐67high group (28% vs. 8%). Median PFS in the Ki‐67low group was 3.1 years, and in the Ki‐67high group 1.6 years (log‐rank p <.001, HR: 1.9). Median OS was not reached in the Ki‐67low vs. 4.8 years in the Ki‐67high cohort (HR: 1.9; log‐rank test: p =.018). In the multivariable modeling, after adjusting for other risk factors, HR for Ki‐67high versus Ki‐67low was 2.4 (p <.001) for PFS and 2.1 (p =.026) for OS. Conclusions: Our results demonstrate that a high Ki‐67 index (>5%) is an independent prognostic marker associated with worse OS and PFS in newly diagnosed MM. IHC staining for Ki‐67 on bone marrow biopsies could be easily adopted as a prognostic biomarker for MM in economically constrained healthcare settings. [ABSTRACT FROM AUTHOR]

Background: This study aimed to compare the diagnostic accuracy of the Ki-67 labeling index (LI) between endoscopic ultrasonography-fine-needle aspiration cytology/biopsy (EUS-FNAC/FNB) and surgical specimens of pancreatic neuroendocrine neoplasms (PanNENs). Methods: Conventional meta-analysis and diagnostic test accuracy (DTA) reviews were performed on 17 eligible studies. The DTA review involved calculating the sensitivity, specificity, diagnostic odds ratio (OR), and area under the curve (AUC) of the summary receiver operating characteristic (SROC) curve. In addition, subgroup analysis was conducted based on EUS-FNAC and FNB, tumor grade, and tumor size. Results: The overall concordance rate of WHO grade based on Ki-67 LI between the EUS-FNAC/FNB and the surgical specimen was 0.767 (95% confidence interval (CI), 0.713–0.814). Concordance rates of the EUS-FNAC and EUS-FNB subgroups were 0.741 (95% CI, 0.681–0.794) and 0.839 (95% CI, 0.738–0.906), respectively. In the DTA review for grade 3, the sensitivity and specificity were calculated to be 0.786 (95% CI, 0.590–0.917) and 0.998 (95% CI, 0.987–1.000), respectively. The diagnostic OR and AUC of the SROC curve were 150.220 (95% CI, 46.145–489.000) and 0.983, respectively. The sensitivity and specificity were observed to be highest in the grade 1 and 3 subgroups, respectively. Conclusions: Higher concordance of tumor grade based on Ki-67 LI was observed between EUS-FNAC/FNB and surgical specimens, indicating the potential usefulness of Ki-67 LI in predicting PanNEN tumor grade in EUS-FNAC/FNB. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to evaluate whether sleep deprivation can induce degenerative changes in rat sublingual glands. Methods: For this purpose, a total of 24 males were distributed into three groups: control (n = 8), in which the animals were not subjected to any procedure; sleep deprivation (n = 8) in which the animals were submitted to sleep deprivation for 96 h; recovery (n = 8), in which the animals were subjected to paradoxical sleep deprivation for 96 consecutive hours followed by 96 h without intervention. Morphological changes in sublingual glands as well as the immunoexpressions of some proteins, such as Ki-67, p16, cleaved caspase-3 and BCL-2 were investigated in this setting. Results: The results showed that paradoxical sleep deprivation induced tissue degeneration as a result of the presence of pyknosis, vacuoles and areas of salivary retention, in the experimental groups. Expression of cleaved caspase 3 and BCL-2 were increased in both sleep deprivation and recovery groups. The analysis of Ki-67 showed an increase in expression only in the recovery group, associated with a decrease in p16 levels. Conclusion: Sleep deprivation can induce a degenerative process in the parenchyma of sublingual gland by means of dysregulation of apoptosis associated with proliferative activity. [ABSTRACT FROM AUTHOR]

Background: Accurate identification of the histopathological grade and the Ki-67 expression level is important in clinical cases of soft tissue sarcomas (STSs). Purpose: To explore the feasibility of a radiomics model based on intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) and diffusion kurtosis imaging (DKI) MRI parameter maps in predicting the histopathological grade and Ki-67 expression level of STSs. Material and Methods: In total, 42 patients diagnosed with STSs between May 2018 and January 2020 were selected. The MADC software in Functool of GE ADW 4.7 workstation was used to obtain standard apparent diffusion coefficient (ADC), D, D*, f, mean diffusivity, and mean kurtosis (MK). The histopathological grade and Ki-67 expression level of STSs were identified. The radiomics features of IVIM and DKI parameter maps were used as the dataset. The area under the receiver operating characteristic curve (AUC) and F1-score were calculated. Results: D -SVM achieved the best diagnostic performance for histopathological grade. The AUC in the validation cohort was 0.88 (sensitivity: 0.75 [low level] and 0.83 [high level]; specificity: 0.83 [low level] and 0.75 [high level]; F1-score: 0.75 [low level] and 0.83 [high level]). MK-SVM achieved the best diagnostic performance for Ki-67 expression level. The AUC in the validation cohort was 0.83 (sensitivity: 0.83 [low level] and 0.50 [high level; specificity: 0.50 [low level] and 0.83 [high level]; F1-score: 0.77 [low level] and 0.57 [high level]). Conclusion: The proposed radiomics classifier could predict the pathological grade of STSs and the Ki-67 expression level in STSs. [ABSTRACT FROM AUTHOR]