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Background/Objectives: One study of pancreatic ductal adenocarcinoma has found expression of glypican-3 (GPC3) and cytokeratin-19 (CK19) determined by immunohistochemistry to be associated with higher stage and grade disease, with a more adverse prognosis. The reported 44% rate of GPC3 expression in pancreatic cancer raises the important possibility that targeted immunotherapies currently in development for hepatocellular carcinoma may also prove useful for GPC3-expressing pancreatic cancers. The present study aims to determine if a similar expression pattern of these markers and stage/grade/prognostic associations is present in our Canadian patient population. Methods: Patients with a pancreatic surgical resection for adenocarcinoma or neuroendocrine tumor (NET) were identified from pathology records over a 5-year period. Immunohistochemistry for GPC3 and CK19 was performed on archived tumor tissue and the proportion of positive cells and intensity of staining were recorded. Grade, stage, and overall survival were compared in patients with NETs that were CK19-positive versus -negative. Results: All 72 pancreatic adenocarcinomas and 20 NETs tested were negative for GPC3, apart from a single case of pancreatic adenocarcinoma. All 72 adenocarcinomas were positive for CK19 expression. Half of the NETs were positive for CK19. There was no correlation between CK19 expression in NETs and tumor grade, lymph node metastasis, distant metastasis, or overall survival. Conclusions: We are skeptical of the reported prognostic value of GPC3 and CK19 in pancreatic adenocarcinomas. CK19 as a prognostic marker in NETs has potential for further study. The results with our protocol for GPC3 immunohistochemistry suggest that pancreatic cancer may be a less promising target for GPC3-targeted immunotherapies than previously thought. [ABSTRACT FROM AUTHOR]

Epithelial progenitor cells of the primitive pancreatic ducts differentiate in 3 directions, which is accompanied by changes in cell phenotype. We analyze the distribution of the pancreatic and duodenal homeobox 1 (PDX1) in the epithelial cells of pancreatic ducts during the prenatal development in order to determine the potential use of this marker as an indicator of pancreatic cell maturation. Pancreatic autopsies from human fetuses (gestation weeks 17-23) were examined by immunohistochemical methods. In general, PDX1 was detected in the epithelial cells that are involved in various morphogenetic processes related to the growth and branching of the fetal pancreatic ducts. The intensive positive reaction to PDX1/cytokeratin 19 indicates immature (progenitor) polypotent ductal cells. [ABSTRACT FROM AUTHOR]

Background: This study aimed to compare the survival outcomes of transarterial chemoembolization (TACE) between patients with early recurrent hepatocellular carcinoma (rHCC) after hepatic resection, stratified by cytokeratin (CK) 19 expression. Methods: A retrospective analysis was conducted on 63 patients with early rHCC after hepatic resection who underwent TACE between January 2017 and December 2021. Patients were divided into two groups based on CK19 expression: CK19-negative (n=31) and CK19-positive (n=32). Overall survival (OS) and progression-free survival (PFS) were compared between the two groups using the Kaplan-Meier method and log-rank test. Cox regression analysis was performed to identify independent risk factors for OS and PFS. Results: The CK19-negative group demonstrated a significantly longer median OS compared to the CK19-positive group (635 days vs. 432 days, p=0.013). Similarly, the CK19-negative group had a longer median PFS than the CK19-positive group (291 days vs. 117 days, p=0.014). Multivariate Cox analysis identified Child-Pugh A grade, CK19-negative expression, and increased TACE sessions as protective factors for OS. No severe TACE-related adverse events were observed. Conclusion: In patients with early rHCC after hepatic resection, those with CK19-positive expression had poorer survival outcomes following TACE compared to CK19-negative patients. These findings suggest the need for additional therapies to improve survival in CK19-positive individuals. [ABSTRACT FROM AUTHOR]

Abstract Background This study aimed to compare the survival outcomes of transarterial chemoembolization (TACE) between patients with early recurrent hepatocellular carcinoma (rHCC) after hepatic resection, stratified by cytokeratin (CK) 19 expression. Methods A retrospective analysis was conducted on 63 patients with early rHCC after hepatic resection who underwent TACE between January 2017 and December 2021. Patients were divided into two groups based on CK19 expression: CK19-negative (n=31) and CK19-positive (n=32). Overall survival (OS) and progression-free survival (PFS) were compared between the two groups using the Kaplan-Meier method and log-rank test. Cox regression analysis was performed to identify independent risk factors for OS and PFS. Results The CK19-negative group demonstrated a significantly longer median OS compared to the CK19-positive group (635 days vs. 432 days, p=0.013). Similarly, the CK19-negative group had a longer median PFS than the CK19-positive group (291 days vs. 117 days, p=0.014). Multivariate Cox analysis identified Child-Pugh A grade, CK19-negative expression, and increased TACE sessions as protective factors for OS. No severe TACE-related adverse events were observed. Conclusion In patients with early rHCC after hepatic resection, those with CK19-positive expression had poorer survival outcomes following TACE compared to CK19-negative patients. These findings suggest the need for additional therapies to improve survival in CK19-positive individuals.

Abstract To analyze the mechanism of how interfering with the cytokeratin 19 (CK19) pathway via the ferroptosis pathway affects tumor biological behaviors in the process of oral squamous cell carcinoma (OSCC) development. TCGA was used to analyze the expression of CK19 in pan-cancer and head and neck squamous cell carcinoma (HNSC) and to explore the ferroptosis-related genes related to HNSC. The effect of silencing CK19 on the migration ability of HSC-4 cells was verified by wound healing and migration assay. HSC-4 cells with silencing of CK19 and tumor-bearing nude mouse model were constructed. RT-qPCR, immunofluorescence and western blot were used to analyze the expression of ferroptosis-related genes. CK19 is highly expressed in human OSCC and nude mice. The migration ability of cells in the CK19-silenced group was lower than that of the control group. In vivo and in vitro, CK19 was negatively correlated with the expression of ACSL4 and positively correlated with the expression of GPX4. Compared with the control group, GPX4 expression was down-regulated and ACSL4 expression was up-regulated in the CK19-silenced group. Silencing CK19 also increased intracellular Fe2+ content and MDA content. Silencing CK19 can affect the expression of GPX4 and ACSL4 to regulate ferroptosis and at the same time increase the content of MDA, Fe2+ and ROS levels, thereby activating the regulation of ferroptosis pathway in the development of OSCC.

Background The incidence of oropharyngeal squamous cell carcinoma (OPSCC) mediated by human papilloma virus (HPV) has been steadily increasing worldwide. The specific pathogenesis of HPV-mediated head and neck squamous cell carcinoma (HNSCC) usually induces carcinogenesis in the oropharynx and the roles of CK7, CK19 and p16 in the carcinogenesis mechanism of HPV-mediated OPSCC still remain uncertain. Methods We collected case data and paraffin samples of 69 cases of OPSCC and 40 cases of OSCC from July 2009 to December 2021. Immunohistochemistry was performed on serial paraffin sections from all cases to analyze the expression patterns of CK7, CK19, and p16. HPV-mediated (p16+) and non-HPV-mediated OPSCC were differentiated based on p16 expression. Three to six fields were selected from each case for observation of the expression intensity, localization, and interrelationship of the three proteins. Results In both cancerous nests and pericancerous normal epithelium of OPSCC, various expression combinations of CK7, CK19 and p16 were observed, including CK7+CK19+p16+, CK7−CK19+p16+, and CK7+CK19+p16−, while no expression of CK7+CK19−p16+ was found. The expression of CK7 with CK19, CK7 with p16, and CK19 with p16 all showed consistency in OPSCC (P < 0.05) while only the expression of CK7 and CK19 demonstrated consistency in OSCC (P < 0.05). The positive rates and H-scores for CK7/CK19 in HPV-mediated (p16+) OPSCC were significantly higher than those in non-HPV-mediated OPSCC and OSCC (P < 0.05). Conclusions These results suggest that CK7, CK19 and p16 may relate to HPV-mediated OPSCC. The interaction of CK7, CK19 and p16 may affect the development of HPV-mediated OPSCC.

Background: The status of the sentinel lymph nodes (SLNs) was an important prognostic factor in varies cancers. A one-step nucleic acid amplification (OSNA) assay, a molecular-based whole-node analysis method based on CK19 mRNA copy number, was developed to diagnose lymph node metastases. We aimed to evaluate the value of OSNA for the diagnosis of sentinel lymph node metastasis in CK19 positive cancers. CK19 mRNA and protein expression for pan-caner analysis were obtained from TCGA and the Human protein atlas database. Methods: Two researchers independently searched the PubMed, Cochrane Library and Web of Science databases for qualified articles published before December 1, 2023. A meta-analysis was performed using MetaDisc and STATA. Risk bias and quality assessments of the included studies were evaluated, and a subgroup analysis was performed. Ten cancer types were found to be CK19 positively expressed and 7 of 10 had been reported to use OSNA for SLN detection. Results: After literature review, there were 61 articles included in the meta-analysis, which consisted of 7115 patients with 18007 sentinel lymph nodes. The pooled sensitivity and specificity of OSNA were 0.87 and 0.95 in overall patients. Moreover, we found the background CK19 expression in normal tissue affected the diagnostic accuracy of OSNA. In breast cancer, we performed subgroup analysis. OSNA exhibited to be a stable method across different population groups and various medical centers. In addition, when 250 copies/μl was chosen as the cutoff point of CK19 mRNA, there were a relatively higher sensitivity and AUC in detecting SLN micro-metastasis than 5000 copies/μl. Discussion: OSNA can predict the occurrence of SLN metastasis accurately in CK19 positive cancers, especially in breast cancer, colorectal cancer, lung cancer, gastric cancer and endometrial cancer. Our study warrants future studies investigating the clinical application of OSNA in pancreatic, ovarian and bladder cancers. [ABSTRACT FROM AUTHOR]

Adrenal cysts lined by thyroid follicular epithelium are rare, with only 14 reported cases of "ectopic thyroid tissue" to date. While the primary consideration for differential diagnosis is thyroid carcinoma metastasis, exclusion of metastases is determined based on the absence of a primary thyroid lesion, serological euthyroidism, lack of thyroglobulin elevation, and absence of epithelial atypia. Herein, we report 2 cases of adrenal cysts lined by thyroid follicular epithelium. Case 1 was a 60-year-old woman with a right adrenal cyst. Case 2 was a 51-year-old man with a left adrenal cyst. Over time, both cysts became larger, necessitating an adrenalectomy. Cystic epithelia were lined with thyroid follicular epithelium, exhibiting moderate atypia. Human bone marrow endothelial cell marker-1 and galectin-3 were focally positive; CK19 was positive in Case 1, and all 3 markers were positive in Case 2, previously reported as an immunophenotype of thyroid carcinoma. CD56 expression was positive in both cases. Targeted next-generation sequencing revealed several low-frequency mutations; however, no major driver alterations for thyroid cancer were detected. Adrenal cysts can be lined by thyroid follicular epithelium. Challenges arise in determining the malignant or benign nature of adrenal cysts. [ABSTRACT FROM AUTHOR]

Low-grade mucoepidermoid carcinoma (MEC) is a salivary gland tumor arising rarely within the jaw bones. It poses a diagnostic challenge due to its considerable overlap of the histopathological features with Glandular odontogenic cyst (GOC). Various theories have been put forward to explain the origin of central low-grade MEC, one of the potential being MEC arising from the lining of GOC. In the present paper we report a case of a multilocular lesion in a 54-year-old female in the mandibular anterior region, which clinically and microscopically had a resemblance to the glandular odontogenic cyst, but the final diagnosis of low-grade MEC was confirmed based on the immunohistochemical appraisal.

BackgroundThe status of the sentinel lymph nodes (SLNs) is an important prognostic factor for many different types of cancer. The one-step nucleic acid amplification (OSNA) assay has emerged as a rapid intraoperative molecular diagnostic tool for LN metastasis detection. We aimed to evaluate and summarize the value of the OSNA assay for the diagnosis of SLN metastasis in cytokeratin 19 (CK19)-positive breast cancer.MethodsTo evaluate the diagnostic value, the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were pooled. The threshold effect, followed by subgroup analysis, was performed to explore the source of heterogeneity. A sensitivity analysis was performed to assess the stability of this meta-analysis model. Fagan plots and likelihood ratio scattergrams were used to explore the potential clinical significance.ResultsA total of 29 eligible studies, which consisted of 5,331 patients with 10,343 SLNs, were included in this meta-analysis. The pooled sensitivity, specificity, PLR, NLR, and DOR were 0.86 (95% CI: 0.85–0.88), 0.94 (95% CI, 0.94–0.95), 18.00 (95% CI, 13.54–23.92), 0.13 (95% CI, 0.10–0.17), and 138.99 (95% CI, 86.66–222.92), respectively. The AUC was 0.97 (95% CI, 0.95–0.98). Sensitivity analysis showed that four studies had an impact on the pooled results and mainly contributed to the heterogeneity. Fagan's nomogram revealed that the prior probability was 50%, the post-probability positive was 95%, and the post-probability negative was 11%.DiscussionOur results suggested that OSNA can predict the occurrence of SLN metastasis in CK19-positive breast cancer. However, more well-designed and multicenter diagnostic tests are needed to validate our results.

Abstract Dual-phenotype hepatocellular carcinoma (DPHCC) is a new subtype of hepatocellular carcinoma (HCC). This study aimed to investigate the relationship between the computerized tomography scan (CT) imaging and clinicopathologic features of DPHCC. The CT imaging and clinicopathologic data of 97 HCC cases who underwent radical resection were collected retrospectively. The CT imaging feature was evaluated by the ratio of the average CT value of tumor to liver (TLR) in the plain scan, arterial, portal vein and delayed phases. The association between CT imaging and clinicopathologic features was analyzed using the t-test or chi-square test. Univariate and multivariate recurrence-free survival (RFS) analysis and overall survival (OS) were performed. The positive rates of cytokeratin 7 (CK7) and CK19 were 35.1% and 20.6% respectively. The positive rate of CK19 was significantly higher in cases with age 4 cm (P = 0.016) or AFP ≥ 400 ng/ml (P = 0.007). The TLR in the portal vein phase was significantly lower in CK19 positive group (P = 0.024). The recurrence risk was significantly higher in cases with CK19 positive (HR: 2.17, 95% CI 1.16 to 4.04, P = 0.013), tumor diameter > 4 cm (HR: 2.05, 95% CI 1.11 to 3.78, P = 0.019), AFP ≥ 400 ng/ml (HR: 2.50, 95% CI 1.37 to 4.54, P = 0.002) or CA199 ≥ 37 U/ml (HR: 2.23, 95% CI 1.12 to 4.42, P = 0.020). However, imaging features, pathological subtype, CK7 or CK19 expression were not significantly related to HCC OS in the univariate and multivariate analysis (all P > 0.05). The expression of CK19 may be associated with the enhancement feature of the portal vein phase CT image, and CK19 positive may suggest a worse RFS.

Cytokeratin 19 (CK19) is a complex intracytoplasmic cytoskeletal protein primarily localized in the ducts of the mammary gland and skin epithelial cells. In humans, the expression of CK19 gene within circulating tumor cells (CTCs) extracted from blood samples of breast cancer patients reflects tumor cell activity, offering valuable insights for predicting early metastatic relapse or monitoring treatment effectiveness. However, knowledge of serum tumor markers is limited in veterinary oncology. Recently, droplet digital PCR (ddPCR), has been employed to explore rare target genes due to its heightened sensitivity and accuracy as a novel molecular diagnostic tool. The objectives of this study were to investigate the expression of the CK19 mRNA in CTCs, non-neoplastic mammary tissues, and both benign and malignant canine mammary tumors (CMTs) through ddPCR analysis. In Study I, we optimized the discard volume for blood samples to reduce CK19 contamination from skin epithelial cells post-venipuncture. The results revealed that discarding the initial 3 mL of blood was adequate and effective in eliminating CK19 mRNA contamination. In Study II, after the removal of the initial 3 mL of blood, we investigated CK19 mRNA-positive CTCs in the peripheral blood of normal healthy dogs, including those with benign and malignant CMTs. Intriguingly, CK19 mRNA was undetectable in all blood samples. The expression of CK19 mRNA in mammary tissues was investigated in Study III. The copy number (CN) ratios of the CK19 gene in non-neoplastic mammary tissues (14.77 ± 14.65) were significantly higher (P < 0.05) than those in benign (4.23 ± 3.35) and malignant groups (6.56 ± 5.64). Notably, no difference was observed between the benign and malignant groups. In conclusion, CK19 mRNA appeared unlikely to be a suitable candidate as a biomarker in the peripheral blood of CMTs, while the CN ratio in mammary tissues could serve as a potential discriminator between non-neoplastic and CMT groups, complementing the gold standard of histopathological examination. • This study pioneers the exploration of the diagnostic potential of CK19 mRNA for canine mammary tumors (CMTs). • The investigation of CK19 mRNA in CMTs involved the application of ddPCR in both blood and tissues. • Significantly minimizing CK19 contamination from skin epithelial cells is achieved by excluding the initial 3 mL of blood. • CK19 mRNA appeared unlikely to be a suitable candidate as a biomarker in the peripheral blood of CMTs. • The copy number ratio of CK19 in mammary tissues may differentiate non-neoplastic and CMT groups. [ABSTRACT FROM AUTHOR]

Background: Gingiva is a delicate tissue that protects alveolar bone against external stimuli. Gingival breaks expose alveolar bone, and the fast wounds heal the betterment of the teeth frame. We aimed to compare the influence of omega-3 on the gingival healing period after trauma and the potential involvement of cytokeratin-19 protein expression. Methods: A total of 18 rabbits were used, after trauma-induced, these rabbits were subdivided into three groups of 6 each. Group 1 is the control group that received normal saline only, the second group received omega 3 for 10 days before the trauma, while the third group received omega 3 supplements for 10 days before the gingival injury and continued receiving them for an additional 10 days afterwards. For each time point (third and seventh day of healing), 3 rabbits were sacrificed, and tissue was collected for total antioxidant capacity and malondialdehyde measurement. Tissue fixed for histopathology and immunohistochemistry analysis. Results: Omega 3 has shown improvement in the healing process regarding the period of healing, antioxidant parameters, and intensity of cytokeratin-19 expression compared to the control group. Moreover, rabbit groups exposed to omega 3 before trauma has shown better healing response compared to those initiated therapy with trauma. Conclusion: Omega 3 is notably beneficial when used for both prevention and treatment since it reduces oxidative stress and improves healing processes measured by increased expression of cytokeratin-19 in epithelial tissue. Omega 3 can therefore be thought of as a possible choice for the treatment of gingival wounds and gingivitis. [ABSTRACT FROM AUTHOR]

Acinar-to-ductal metaplasia (ADM) has been shown to contribute to the development of pancreatic ductal adenocarcinoma (PDAC) in genetically engineered mouse models, but little is known about whether acinar cell plasticity contributes to carcinogenesis in human PDAC. We aimed to assess whether cancer cells that stain positive for amylase and CK19 (ADM-like cancer cells) are present in human resected PDAC and to investigate their role in tumor progression. We immunohistochemically investigated the presence of ADM-like cancer cells, and compared the clinical and histological parameters of PDAC patients with and without ADM-like cancer cells. ADM-like cancer cells were detected in 16 of 60 (26.7%) PDAC specimens. Positive staining for anterior gradient protein 2 (AGR2) was observed in 14 of 16 (87.5%) PDAC specimens with ADM-like cancer cells. On the other hand, the intensity of AGR2 expression (negative, low/moderate or high) was lower in PDAC with ADM-like cancer cells (9/7) than in PDAC without these cells (11/33) (P = 0.032). The presence of ADM-like cancer cells was significantly correlated with increased cell proliferation (P = 0.012) and tended to be associated with MUC1 expression (P = 0.067). These results indicated that acinar cells may act as the origin of human PDAC, and that their presence may be useful for the stratification of human PDAC to predict prognosis. [ABSTRACT FROM AUTHOR]

Aim: Our aim in this retrospective study is to evaluate the factors that are important in the prognosis of thyroid papillary microcarcinoma. Material and Method: This study is a retrospective study. In the study, 277 thyroid papillary microcarcinoma nodules belonging to 178 patients, diagnosed in Kütahya University of Health Sciences Hospital, between 2010 and 2020, were included. The prognostic significance of tumor diameter, unilaterality, bilaterality, multifocality, number of tumor foci, fibrosis, distance from the capsule and Gal-3, HBME-1 and CK19 staining were investigated retrospectively by comparing with negative prognostic factors such as lymphovascular invasion, lymph node metastasis, capsular invasion and extrathyroidal spread. Moreover, the relationship between immunostains and fibrosis was examined. Results: The significant association was found between >0.5 tumor diameter and lymph node metastasis. Unilaterality, bilaterality, multifocality and number of tumor foci was associated with lymphovascular invasion and lymph node metastasis. Fibrosis was associated with capsular invasion and extrathyroidal spread. A correlation was found between the prevalence of Gal- 3 and capsular invasion and extrathyroidal spread, and between the prevalence of CK-19 and lymph node metastasis. A positive correlation was found between fibrosis and Gal-3 and CK19, and negative correlations with HBME-1 intensity. Conclusion: Negative prognostic markers are >0.5 tumor diameter, unilaterality, bilaterality, multifocality, number of tumor foci, fibrosis, Gal-3 and CK19 prevalence. A positive correlation was found between fibrosis and Gal-3 and CK19, and negative correlation with HBME-1 intensity.

Introduction: Thyroid cancer is the most common type of endocrine cancer, with an increasing prevalence. The possibility of a malignant neoplasm is the primary concern in people with thyroid nodules. The presence of a plethora of variants complicates the diagnostic process. Cytokeratin 19 (CK19), found in normal thyroid follicular epithelium, is upregulated during neoplastic transformation, and CD56, a neural cell adhesion molecule, is downregulated in thyroid follicular cells. This study suggests the use of CK19 and CD56 in combination will help differentiate thyroid neoplasms. Materials and Methods: Total/hemithyroidectomy specimens received in the Department of Pathology, Maharaja Krushna Chandra Gajapati Medical College and Hospital, Brahmapur, Odisha, India, suspected of malignancy, were processed for routine histopathological evaluation using hematoxylin and eosin (H&E) stain and immunohistochemistry (IHC) staining using CK19 and CD56. The outcomes of each case were recorded and analyzed. Results: A total of 36 cases were evaluated, and the expression of CK19 was found to be 88% sensitive and 79% specific in differentiating malignant from benign thyroid neoplasms. The absence of CD56 expression was found to have 82% sensitivity and 74% specificity in detecting malignant thyroid neoplasms. The combined use of both markers has a sensitivity and specificity of 70.59% and 78.95%. Conclusion: The routine use of CK19 and CD56 by IHC will aid in distinguishing benign from malignant thyroid neoplasms.

OBJECTIVE: The goal of this study was to look at the patterns of thyroid tumors and how thyroid cancer markers showed up in immunohistochemistry in Northern Saudi Arabia. PATIENTS AND METHODS: This study investigated retrospectively 190 patients who attended with thyroid complaints. About 140 thyroid biopsies were diagnosed in the Department of Pathology at King Salman Hospital, Ha’il, from November 2019 to November 2020. RESULTS: Out of the 190 patients who attended with thyroid complaints, 140/190 (73.7%) were detected with thyroid lesions (58 malignant and 82 benign). Benign lesions included goiter 49/82 (60%), follicular adenoma 17/82 (21%), Hashimoto’s thyroiditis 13/82 (16%), and toxic goiter 3/82 (3%). 5/6 (83.3%) of males with benign lesions had goiters. CK19 was positive in 68.5% of the cases; 71.8% were papillary, 66.7% were follicular, and 100% were undifferentiated carcinomas. Out of the 26/54 (48%) CD56-positive cases, 18/39 (46%) were papillary, 7/12 (58.3%) were follicular, and 3/3 (100%) were undifferentiated carcinomas. Out of the 35/54 (64.8%) Galectin-3-positive cases, 69.2% were papillary, 7/12 (58.3%) were follicular, and 3/3 (100%) were undifferentiated carcinomas. CONCLUSIONS: Thyroid cancer is prevalent in northern Saudi Arabia, with the predominant type being papillary thyroid carcinoma. Most patients are female and younger. The combined use of CK19, CD56, and Galectin-3 tumor markers assists in the accurate differential diagnosis of thyroid neoplasms. [ABSTRACT FROM AUTHOR]

To investigate the predictive value of gadoxetic acid-enhanced magnetic resonance imaging (MRI) features on the pathologic grade, microvascular invasion (MVI), and cytokeratin-19 (CK19) expression in hepatocellular carcinomas (HCC), and to evaluate their association with postoperative recurrence of HCC. This retrospective study included 147 patients with surgically confirmed HCCs who underwent gadoxetic-enhanced MRI. The lesions were evaluated quantitatively in terms of the relative enhancement ratio (RER), and qualitatively based on imaging features and clinical parameters. Logistic regression analyses were performed to investigate the value of these parameters in predicting the pathologic grade, MVI, and CK19 in HCC. Predictive factors for postoperative recurrence were determined using a Cox proportional hazards model. Peritumoral enhancement (odds ratio [OR], 3.396; p = 0.025) was an independent predictor of high pathologic grades. Serum protein induced by vitamin K absence or antagonist (PIVKA) level > 40 mAU/mL (OR, 3.763; p = 0.018) and peritumoral hypointensity (OR, 4.343; p = 0.003) were independent predictors of MVI. Predictors of CK19 included serum alpha-fetoprotein (AFP) level > 400 ng/mL (OR, 4.576; p = 0.005), rim enhancement (OR, 5.493; p = 0.024), and lower RER (OR, 0.013; p = 0.011). Peritumoral hypointensity (hazard ratio [HR], 1.957; p = 0.027) and poor pathologic grades (HR, 2.339; p = 0.043) were independent predictors of recurrence. We demonstrated the value of preoperative gadoxetic-enhanced MRI in predicting aggressive pathological features of HCC. Poor pathologic grades and peritumoral hypointensity may independently predict the recurrence of HCC. [ABSTRACT FROM AUTHOR]

Background: The differential diagnosis of intrahepatic cholangiocarcinomas (iCCAs) from metastatic adenocarcinomas from organs adjacent to the liver (gallbladder, pancreas, and stomach) is difficult due to histopathological similarity and a lack of specific markers. This study aimed to develop a method to differentiate iCCA and adenocarcinomas originated from extrahepatic organs adjacent to the liver. Methods: We retrospectively enrolled surgically resected iCCA (n = 181) and adenocarcinomas from extrahepatic organs (n = 30, n = 28, and n = 38 from gallbladder, pancreas, and stomach, respectively) between 2007 and 2013. The albumin mRNA in situ hybridization (ISH) and immunohistochemistry (IHC) of filamin-A and cytokeratin 19 (CK19) were performed using tissue microarray. Using logistic regression analysis of three markers, iCCA-score was developed, and its diagnostic performance was evaluated. Results: The iCCAs were more frequently positive for albumin ISH (23.2% vs. 0%), filamin-A IHC (47.5% vs. 12.5%) and CK19 (68.5% vs. 40.6%) than extrahepatic adenocarcinomas (p < 0.001 for all). The iCCA-score consisting of these three markers was developed, and it showed higher diagnostic performance (area under the curve [AUC], 0.798 vs. 0.616, p < 0.001). Taking an iCCA-score of 2 or higher as the threshold for iCCA, the sensitivity was substantially higher than albumin ISH alone (45.9% and 23.2%, respectively; p < 0.001), but maintained high specificity (94.8% and 100%, respectively). Conclusion: Albumin ISH and IHC staining for filamin-A and CK19 showed distinct expression patterns between iCCA and extrahepatic adenocarcinomas from gallbladder, pancreas, and stomach. We developed iCCA-score that consisted of those three markers, and it showed better diagnostic performance than albumin ISH alone. [ABSTRACT FROM AUTHOR]

Background: The most prevalent type of thyroid cancer is papillary thyroid carcinoma. PTC's unique nuclear properties are the primary diagnostic indicator. It is difficult to make a diagnosis since similar lesions are focally present in other thyroid lesions. Aim: The ability of the immunohistochemical markers CD56 and CK19 (cytokeratin 19) to identify papillary thyroid carcinoma from similar thyroid lesions. Methods: We looked at 122 instances of various thyroid lesions in the population of Iraq where CK19 and CD56 immunoexpression was detected. The study was carried out on the clinical evaluation, responsiveness, precision, and predictive positive and negative values. Results: CK19 was strongly expressed in 89.7% of the PTC group and strongly negative in 85.7% of the NPTC group, per the statistical findings (P<0.001). CD56 expression was significantly (P<0.001) reduced in more individuals of the PTC group by 97.2%). CK19 was the most sensitive marker and CD56 was the most specific marker when comparing papillary carcinoma with thyroid hyperplastic diseases, and diagnostic accuracy was improved when both markers were combined. In terms of papillary Micro carcinoma stain, CK 19 had 100% prevalence and 100% sensitivity, whereas CD56 had 100% specificity. Conclusion: In order to diagnose papillary thyroid carcinoma and distinguish it from its mimics, immunohistochemistry using the markers CK19 and CD56 is a recognized effective supplementary method in questionable cases. [ABSTRACT FROM AUTHOR]

Abstract Background Lymph node (LN) status is a key prognostic factor in the decision-making process of different cancer entities, including prostate cancer (PCa). Sectioning and haematoxylin and eosin (H&E) staining technique remain the gold standard for the evaluation of LN metastases despite some limitations, especially low sensitivity in detecting an accurate tumour burden within the LN, as well as a subjective and time-consuming result. One-step nucleic acid amplification (OSNA) quantifies mRNA copies of cytokeratin 19 (CK19) in a fast, objective, automated, and reproducible way, raising a general interest to explore its utility for lymphatic metastasis identification in different malignancies. Methods To present the latest evidence related to the detection of LN metastases in several tumours by using OSNA compared with the conventional H&E method, a systematic review of articles published since March 2021 was conducted using PubMed, Cochrane Library, and Web of Science databases. References from primary papers and review articles were checked to obtain further potential studies. Our procedure for evaluating records identified during the literature search followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses criteria. With the aim to design and justify future clinical routine use of OSNA in PCa, novel PCa evidence has been included in this review for the first time. Results Twenty five studies were included. LN from six different groups of tumours: breast, gastrointestinal, gynecological, lung, head and neck and prostate cancers has been assessed. OSNA was compared with post-operative formalin-fixed paraffin-embedded tissue sections with H&E staining as the reference standard. Contingency tables were created, and concordance rate, sensitivity, specificity and predictive values were reported. Seventeen studies analysed the discordant cases using different techniques. Conclusion OSNA method has a high diagnostic accuracy for the detection of LN metastases in several CK19 expressing tumours. Available evidence might encourage future investigations about its usage in PCa patients to improve LN staging and prognosis.

Background: In hepatocellular carcinoma (HCC), CK19 is a marker of hepatic progenitor cells and acts as a key player in tumor invasion, indicating poor prognosis. Early diagnosis of HCC heavily affects the clinical outcome of patients. The widely accepted serological marker for HCC diagnosis is alpha-fetoprotein (AFP). However, its diagnostic accuracy is controversial and unsatisfactory because of its low sensitivity. The objective of the current study is to evaluate the influence of CK19 level on Pattern of HCC in patients with liver cirrhosis. Patients and methods: This was a prospective case -control study that was conducted on patients attending at early detection of HCC Outpatient Clinic or admitted to Hepatology and Gastroenterology Unit, Specialized Medical Hospital Mansoura University, over past year. The current study included 75 participants divided into 3 groups: Group 1 (HCC), Group 2 (cirrhosis only) and Group 3 (healthy people without any medical disease). Results: There was statistically significant increase as regard median CK19 level, between degrees of aggressiveness index (A, B and C) (P >0.05). Regarding the validity of CK19 in differentiating the studied groups, there was no statistically significant difference as regard median CK19 level in cirrhosis and control groups with Sensitivity 56% and Specificity 40%. There was no statistically significant difference as regard median CK19 level in HCC and control groups with Sensitivity 64% and Specificity 40%. There was no statistically significant difference as regard median CK19 level in HCC and cirrhosis groups with Sensitivity 64% and Specificity 44%. There is weak significant relationship between the levels of CK19 and AFP in HCC cases (P-value 0.07). Conclusion: CK19 associated carry a poor prognosis as it associated with more aggressive pattern of HCC. CK19 is good negative marker of early HCC, So CK19 negative HCC patients has no priority for treatment. [ABSTRACT FROM AUTHOR]

Background: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) mediated by human papilloma virus (HPV) has been steadily increasing worldwide. The specific pathogenesis of HPV-mediated head and neck squamous cell carcinoma (HNSCC) usually induces carcinogenesis in the oropharynx and the roles of CK7, CK19 and p16 in the carcinogenesis mechanism of HPV-mediated OPSCC still remain uncertain., Methods: We collected case data and paraffin samples of 69 cases of OPSCC and 40 cases of OSCC from July 2009 to December 2021. Immunohistochemistry was performed on serial paraffin sections from all cases to analyze the expression patterns of CK7, CK19, and p16. HPV-mediated (p16+) and non-HPV-mediated OPSCC were differentiated based on p16 expression. Three to six fields were selected from each case for observation of the expression intensity, localization, and interrelationship of the three proteins., Results: In both cancerous nests and pericancerous normal epithelium of OPSCC, various expression combinations of CK7, CK19 and p16 were observed, including CK7+CK19+p16+, CK7-CK19+p16+, and CK7+CK19+p16-, while no expression of CK7+CK19-p16+ was found. The expression of CK7 with CK19, CK7 with p16, and CK19 with p16 all showed consistency in OPSCC ( P < 0.05) while only the expression of CK7 and CK19 demonstrated consistency in OSCC ( P < 0.05). The positive rates and H-scores for CK7/CK19 in HPV-mediated (p16+) OPSCC were significantly higher than those in non-HPV-mediated OPSCC and OSCC ( P < 0.05)., Conclusions: These results suggest that CK7, CK19 and p16 may relate to HPV-mediated OPSCC. The interaction of CK7, CK19 and p16 may affect the development of HPV-mediated OPSCC., Competing Interests: The authors declare that they have no competing interests., (© 2024 Yan et al.)

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Background: 5-Hydroxymethylcytosine (5hmC) with dynamic existence possesses multiple regulatory functions. Whereas, 5hmC’s impact on small hepatocellular carcinoma (SHCC) remains unclear. The present work focused on characterizing 5hmC content within SHCC and assessing the possibility of using global genomic 5hmC level as the predicative factor of clinical outcome. Methods: This study applied ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) in measuring 5mC, 5fC and 5hmC contents. In addition, immunohistochemistry (IHC) was adopted to measure CK19 and 5hmC contents. Results: Research showed 5mC, 5hmC, and 5fC contents from global genomics of SHCC reduced extensively compared with healthy samples (p < 0.001). Moreover, SHCC was associated with lymph node metastasis (LNM). Greater 5mC and 5hmC levels were observed in non-metastasis group compared with the metastasis group (p < 0.001). Correlation analysis between the HBV DNA level and 5mC, 5fC and 5hmC levels exhibited that HBV DNA was associated with 5mC, 5hmC, and 5fC content reduction, which was verified in the cytological experiments. Moreover, 5hmC content had a negative correlation with the expression level of CK19 in SHCC. The decrease in 5hmC and CK19 containing 5hmC positive cell (called CK195hmC+) should be ascribed to the bad prognosis among SHCC patients. Conclusions: The contents of 5hmC and CK195hmC+ of genomic DNA might be adopted for predicting SHCC survival as an important biomarker.

Abstract Background Thyroid neoplasms with follicular architecture can have overlapping morphologic features and pose diagnostic confusion among pathologists. Various immunohistochemical stains have been investigated as potential diagnostic markers for PTC, among which HBME1 and CK19 have gained popularity. Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) poses similar diagnostic challenges with interobserver variability and is often misdiagnosed as adenomatoid nodule or follicular adenoma. This study aims to evaluate expression of HBME1 and CK19 in NIFTPs in comparison to other well-differentiated thyroid neoplasms and benign mimickers. Method Seventy-three thyroid cases diagnosed over a period of 3 years at Methodist University Hospital, Memphis, TN, USA, were included in this study: 9 NIFTP; 18 papillary thyroid carcinoma (PTC); 11 follicular variant of papillary thyroid carcinoma, invasive (I-FVPTC); 24 follicular adenomas (FA); and 11 multinodular goiters/adenomatoid nodules (MNG). A tissue microarray (TMA) was constructed and HBME1 and CK19 immunohistochemistry was performed. Results 77.8% of NIFTPs, 88.9% of PTCs, 81.8% of I-FVPTCs, 16.7% of FAs, and 18.2% of MNGs showed HBME-1 expression. 66.7% of NIFTPs, 83.3% of PTCs, 81.8% of I-FVPTCs, 33.3% of FAs, and 45.4% of MNGs expressed CK19. Difference in expression of HBME1 and CK19 was statistically significant for NIFTP vs FA (qualitative; p < 0.05) and NIFTP vs MNG (p < 0.05). No statistically significant difference was found for HBME1 in NIFTP vs PTC (conventional and FVPTC), p ≥ 0.2. Sensitivity of HBME1 and CK19 for NIFTP were 78% and 67%, ~ 88% each for PTC, and 89% and 100% for FVPTC, respectively, while specificity of HBME1 and CK19 for NIFTP were 53% each, ~ 62% each for PTC, and ~55% each for FVPTC. Conclusion Our study indicated that HBME1 and CK19 are valuable markers in differentiating NIFTPs from morphologic mimics like follicular adenoma and adenomatoid nodules/multinodular goiter. While HBME1 and CK19 are both sensitive in diagnosing lesions with PTC-like nuclear features, CK19 stains a higher number of benign lesions in comparison to HBME1. No increase in sensitivity or specificity in diagnosis of NIFTP, PTC, or FVPTC was noted on combining the two antibodies.

Background: Thyroid neoplasm is one of the most common endocrine neoplasms. The diagnosis and the distinction between malignant and benign neoplasms can be difficult, but it has clinical, therapeutic, and prognostic significance. Hence, it is necessary to make precise diagnosis by using biomarkers. Materials and Methods: This is a laboratory observational study considering histologically diagnosed cases of papillary thyroid carcinoma (PTC) and nonneoplastic thyroid lesions. Immunohistochemistry (IHC) staining was done on tissue sections of all cases for CK19 and galectin-3 using appropriate positive and negative controls. The expression of immunomarkers was evaluated by a semi-quantitative method as negative, weak positive, moderate positive, and strong positive. The data were entered in Microsoft Excel sheet and were analyzed using SPSS 22 version software. Results: A total of 52 cases were considered for the study, of which 26 cases each were PTC and nonneoplastic lesions of thyroid. Among the 26 PTC cases, 6 were classical variant of PTC (CVPTC) and 20 were follicular variant of papillary thyroid carcinoma (FVPTC). Among 26 nonneoplastic cases, 13 each were nodular hyperplasia cases and lymphocytic thyroiditis. There was a statistically significant (P < 0.01) association of CK19 and galectin-3 expression between CVPTC and FVPTC. There was no statistically significant association (P = 0.271) of CK19 expression between PTC and nonneoplastic cases. There was a statistically significant association (P = 0.003) of galectin-3 expression between PTC and nonneoplastic cases. Conclusion: Galectin-3 expression can be used to differentiate PTC from nonneoplastic lesions of thyroid in ambiguous cases. Galectin-3 and CK19 expression can be used to classify PTC into CVPTC and FVPTC. [ABSTRACT FROM AUTHOR]

Background: Lymph node (LN) status is a key prognostic factor in the decision-making process of different cancer entities, including prostate cancer (PCa). Sectioning and haematoxylin and eosin (H&E) staining technique remain the gold standard for the evaluation of LN metastases despite some limitations, especially low sensitivity in detecting an accurate tumour burden within the LN, as well as a subjective and time-consuming result. One-step nucleic acid amplification (OSNA) quantifies mRNA copies of cytokeratin 19 (CK19) in a fast, objective, automated, and reproducible way, raising a general interest to explore its utility for lymphatic metastasis identification in different malignancies.Methods: To present the latest evidence related to the detection of LN metastases in several tumours by using OSNA compared with the conventional H&E method, a systematic review of articles published since March 2021 was conducted using PubMed, Cochrane Library, and Web of Science databases. References from primary papers and review articles were checked to obtain further potential studies. Our procedure for evaluating records identified during the literature search followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses criteria. With the aim to design and justify future clinical routine use of OSNA in PCa, novel PCa evidence has been included in this review for the first time.Results: Twenty five studies were included. LN from six different groups of tumours: breast, gastrointestinal, gynecological, lung, head and neck and prostate cancers has been assessed. OSNA was compared with post-operative formalin-fixed paraffin-embedded tissue sections with H&E staining as the reference standard. Contingency tables were created, and concordance rate, sensitivity, specificity and predictive values were reported. Seventeen studies analysed the discordant cases using different techniques.Conclusion: OSNA method has a high diagnostic accuracy for the detection of LN metastases in several CK19 expressing tumours. Available evidence might encourage future investigations about its usage in PCa patients to improve LN staging and prognosis. [ABSTRACT FROM AUTHOR]

Cytokeratin19 (CK19) was detected as the most related marker for circulating tumor cells, which was assessed in specific cell lines. MCF7, SKBR3, T47D, and MDA-MB-231, and HeLa cell line as negative control were used. CK19 expression was confirmed by using mouse monoclonal anti-human CK19 antibody. CK19 detection in MDA-MB-231 was not observed. CK19 marker expression was compared in T47D, MCF7, and SKBR3 cell lines. T47D and MCF7 belonged to the luminal subtype of breast cancer (BC) that CK19 expression regulated with an ER marker. SKBR3 belonged to the HER2 positive subtype of BC. However, MDA-MB-231 belonged to the claudin-low subtype of BC that lack of CK19 expression strongly is related to negative ER, PR, and HER2. Therefore, there are not only quantitative differences in CK19 expression, but its expression could also link to the other markers of BC that should be considered in the molecular classification of breast carcinoma. Different expression levels related to cell classification could be useful in the prognosis and treatment of cancers with epithelial origins. [ABSTRACT FROM AUTHOR]

Introduction: Cytokeratin 19 (CK19) is highly expressed in epithelial tumours such as breast cancer (BC). Octamer-binding transcription factor 4 (OCT4), a transcription factor of the POU (Pit-Oct-UNC) family, plays a critical role in the self-renewal and maintenance of pluripotency of embryonic stem cells; therefore, it has been used as a promising CSC marker. Material and methods: CK19 was assessed in peripheral blood using flow-cytometric analysis while OCT4 was evaluated in breast tissue samples by immunohistochemistry from 70 patients (non-metastatic BC, metastatic BC, and non-malignant breast tumours). Results: CK19 and OCT4 were significantly associated with BC patients compared to control (p < 0.001). CK19 was detected in 38 patients with BC (62.2%); meanwhile, OCT4 was positive in 37 BC patients (60.6%). CK19 was positively associated with grade (p = 0.002), HER2 (p = 0.009), metastasis (p = 0.026), molecular subtypes and LN (p < 0.001), and stage (p = 0.001) while OCT4 expression was positively associated with BMI (p < 0.023), aggressive molecular subtype (p < 0.019), ER expression (p = 0.025), presence of LN metastases (p < 0.017), and distant metastasis (p < 0.018). A non-significant relation was found between the expression of CK19 and OCT (p = 0.291). The positive expression of CK19 and OCT4 was significantly and inversely associated with both 3-year OS and 3-year PFS. Conclusions: CK19 and OCT4 are associated with BC, so they can be considered as prognostic and predictive markers for poor OS and PFS in non-metastatic as well as metastatic BC patients. [ABSTRACT FROM AUTHOR]

One of the key parameters in the diagnosis of papillary thyroid carcinoma (PTC) are true nuclear pseudoinclusions (NPs), which constitute invaginations of the cytoplasm into the nucleus. On the other hand, strong cytoplasmic expression of CK19 is a well-known attribute of PTC tumor cells. We analyzed NPs using CK19 immunohistochemistry in histological sections of 52 PTCs and seven noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTPs). Strong CK19+ NPs were present in 77% of PTCs, whereas NPs in hematoxylin and eosin (HE)-stained slides (HE NPs) were identified in only 48% of PTCs. Detection of CK19+ NPs enabled easier and objective recognition of NPs and better discrimination of NPs from pseudo-pseudoinclusions than detection of HE NPs. In the 15 of the 27 (55.5%) PTCs in which we could not discern HE NPs, strong CK19+ NPs could be identified reliably, quickly and easily. Moreover, all NIFTPs were negative for both CK19+ NPs and HE NPs. Detection of CK19+ NPs may refine the assessment of this important diagnostic feature and, hence, the microscopic diagnostic criteria of PTC. Thus, these findings may have implications for the accurate diagnosis of PTC and NIFTP.

Detection of thyroid carcinoma has been steadily increased in the past few decades. After the recognition of NIFTP, also gain importance to differentiate benign tumors (follicular adenoma) from follicular patterned variants of papillary thyroid carcinoma (invasive and infiltrative follicular variant papillary thyroid carcinoma), and low-risk lesions of thyroid (NIFTP). Follicular patterned proliferations of thyroid still persists as a battle for pathologists. In this study, we aimed to analyze the most commonly used immunohistochemical stains “HBME1, CK19, Galectin-3”, adding the new ones “CD56, CD57, and p63”. Study groups were; nodular hyperplasia, follicular adenoma, NIFTP, infiltrative follicular variant PTC, classical variant PTC (CVPTC) and follicular carcinoma. Each group consisted of twenty cases. The sections were stained with CD56, CD57, p63, CK19, HBME1 (Mesotel cell), Galectin-3 antibody. Although the expression of CD56 was high in benign follicular lesions, FC could not be excluded in this group. CD57 was high in malignant follicular group and NIFTP. Interestingly, p63 was found highly expressed in FVPTC, which might be promising to predict invasiveness in follicular group of lesions. CK19, Galectin-3 and HBME1 were found quietly prominent in CVPTC in concordance with the previous reports.

Background: The status of the sentinel lymph nodes (SLNs) is an important prognostic factor for many different types of cancer. The one-step nucleic acid amplification (OSNA) assay has emerged as a rapid intraoperative molecular diagnostic tool for LN metastasis detection. We aimed to evaluate and summarize the value of the OSNA assay for the diagnosis of SLN metastasis in cytokeratin 19 (CK19)-positive breast cancer., Methods: To evaluate the diagnostic value, the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were pooled. The threshold effect, followed by subgroup analysis, was performed to explore the source of heterogeneity. A sensitivity analysis was performed to assess the stability of this meta-analysis model. Fagan plots and likelihood ratio scattergrams were used to explore the potential clinical significance., Results: A total of 29 eligible studies, which consisted of 5,331 patients with 10,343 SLNs, were included in this meta-analysis. The pooled sensitivity, specificity, PLR, NLR, and DOR were 0.86 (95% CI: 0.85-0.88), 0.94 (95% CI, 0.94-0.95), 18.00 (95% CI, 13.54-23.92), 0.13 (95% CI, 0.10-0.17), and 138.99 (95% CI, 86.66-222.92), respectively. The AUC was 0.97 (95% CI, 0.95-0.98). Sensitivity analysis showed that four studies had an impact on the pooled results and mainly contributed to the heterogeneity. Fagan's nomogram revealed that the prior probability was 50%, the post-probability positive was 95%, and the post-probability negative was 11%., Discussion: Our results suggested that OSNA can predict the occurrence of SLN metastasis in CK19-positive breast cancer. However, more well-designed and multicenter diagnostic tests are needed to validate our results., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Wang and Wang.)

Overdiagnosis of papillary thyroid hyperplasia which may mimic papillary thyroid carcinoma in fine‐needle aspiration and frozen section has a serious impact on the patient. Therefore, it is important to know the difference between them to avoid over or undertreatment. [ABSTRACT FROM AUTHOR]

Background: 5-Hydroxymethylcytosine (5hmC) with dynamic existence possesses multiple regulatory functions. Whereas, 5hmC’s impact on small hepatocellular carcinoma (SHCC) remains unclear. The present work focused on characterizing 5hmC content within SHCC and assessing the possibility of using global genomic 5hmC level as the predicative factor of clinical outcome. Methods: This study applied ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) in measuring 5mC, 5fC and 5hmC contents. In addition, immunohistochemistry (IHC) was adopted to measure CK19 and 5hmC contents. Results: Research showed 5mC, 5hmC, and 5fC contents from global genomics of SHCC reduced extensively compared with healthy samples (p < 0.001). Moreover, SHCC was associated with lymph node metastasis (LNM). Greater 5mC and 5hmC levels were observed in non-metastasis group compared with the metastasis group (p < 0.001). Correlation analysis between the HBV DNA level and 5mC, 5fC and 5hmC levels exhibited that HBV DNA was associated with 5mC, 5hmC, and 5fC content reduction, which was verified in the cytological experiments. Moreover, 5hmC content had a negative correlation with the expression level of CK19 in SHCC. The decrease in 5hmC and CK19 containing 5hmC positive cell (called CK195hmC+) should be ascribed to the bad prognosis among SHCC patients. Conclusions: The contents of 5hmC and CK195hmC+ of genomic DNA might be adopted for predicting SHCC survival as an important biomarker. [ABSTRACT FROM AUTHOR]

Background: Calcifying epithelial odontogenic tumor (CEOT) is a benign but locally aggressive epithelial odontogenic tumor that most commonly occurs in the mandible. Although the maxillary CEOT is rare, its biological behavior is indolent. Aim: A comprehensive immunohistochemical study was performed concerning the local aggressive behavior of this tumor. Patients and methods: In this study, 12 cases of patients who were attended in the outpatient clinic of the Oral and Maxillofacial Department, Faculty of Dentistry, Tanta University were included in this study after confirmed incisional biopsy of CEOT. The patients were examined clinically preoperative and aspiration test was done. After finishing the tumor resection, closure of the maxillary defect was done by double layer repair of the defect. Biopsy of this tumor was stained by the following markers p63, Ki67, type IV collagen, smooth muscle actin (SMA), CK19, CK5/6, S100 to study the biological behavior of the tumor. Results: The neoplastic cells were diffusely cytoplasmic immunoreactive for CK19 and CK5/6. Also, the tumor cells showed mild to moderate staining to SMA. Weak intensity of collagen type IV was detected. The amyloid-like deposit was immunonegative for both SMA and type IV collagen. p63 was expressed in all studied cases. Strong to moderate nuclear staining to p63 was detected in the tumor cells. The Ki67 showed high proliferation activity of tumor cells differing from the benign tumor nature. Conclusion: Maxillary CEOT tends to grow more rapidly and not be circumscribed, suggesting that more aggressive surgery is required in these specific cases. [ABSTRACT FROM AUTHOR]

Abstract Overdiagnosis of papillary thyroid hyperplasia which may mimic papillary thyroid carcinoma in fine‐needle aspiration and frozen section has a serious impact on the patient. Therefore, it is important to know the difference between them to avoid over or undertreatment.

Objective: To determine the predictive value of cytokeratin 19 (CK19) for evaluating the safety of ovarian preservation in patients with endometrial cancer (EC).Methods: Five hundred and seventeen EC patients hospitalized from November 2010 to June 2016 were reviewed retrospectively. Pre-operative tumor biomarkers including CA125, HE4, CK19, and CA19-9 were obtained. Predictive biomarkers associated with ovarian metastasis were selected using univariate and multivariate Logistic regression. The cut-off values were determined by receiver operating characteristic (ROC) curves. Kaplan-Meier method and Cox multivariate regression model was used to perform survival analysis.Results: Among clinical parameters and biomarkers included, age > 65, type II EC, CA125 ≥ 35 u/ml, CK19 > 3.3 ng/ml, and myometrial invasion ≥ 50% depth appeared as significant predictors of the risk of ovarian involvement in univariable logistic analysis. In multivariable analysis, CK19 > 3.3 ng/ml (OR = 11.541, 95%CI: 1.968–67.668, P = 0.007) and Type II EC (OR = 8.336, 95%CI: 1.456–47.722, P = 0.017) were independent risk predictors of ovarian metastasis in pre-menopausal women. In pre-menopausal women with Type I EC (n = 142), CK19 level could satisfactorily predict the risk of ovarian metastasis (AUC = 0.860, 95%CI: 0.792–0.912, P < 0.001), and when the cut-off point was set as 2.45 ng/ml, the negative predictive value and negative likelihood ratio were 99% and 0.19, with the maximum Youden index of 0.598.Conclusions: The present study advocates the necessity of incorporating serum CK19 measurement into the pre-operative evaluation of EC, especially as extension of current standard approach with ovarian preservation counseling.

Diabetes Mellitus (DM) manifests itself with changes in the functional structure of the lungs and impairments in gas exchange. These changes in diabetic lung tissue may be due to various factors. Our aim in this study is to correlate the damage of diabetes with lung tissue in terms of VEGF, CK19, caspase 3 immunolocalizations. In this study, animals were divided into 4 groups, 60 mg/kg streptozotocin was given to each of the groups with experimental diabetes and the physiological saline solution was given intraperitoneally to the control group. On days 7 and 14 of the experiment, diabetic and control groups were euthanized, and lung tissues were removed. Tissue samples were evaluated histochemically and immunohistochemically by monitoring with standard light microscopy. In the diabetic group, the localization of CK19 and Caspase 3 increased on the 7th and 14th days compared to the control group, but the immunolocalization of VEGF decreased. Based on our findings, it was determined that lung tissue was one of the target organs of diabetes. The increase in pulmonary parenchyma due to hyperglycemia is accepted as a source of fibrosis. We concluded that due to increased CK19 localization of fibrosis source, decreased VEGF localization has increased apoptosis in the pulmonary capillary endothelium, which has a significant role in the blood-air barrier in the lung parenchyma, especially in endothelial cells.

Context: Well-differentiated tumor of uncertain malignant potential (WDT-UMP) were encapsulated follicular pattern tumors with diffuse equivocal or focal unequivocal papillary thyroid carcinoma (PTC) type nuclear changes without definite invasion. These tumors are suggested to be borderline in its nature. Immunohistochemistry by CD56, P63, and CK19 are common markers used in differentiation between benign and malignant thyroid tumor. Computerized nuclear morphometry is an inexpensive objective and reproducible tool to evaluate histological features of thyroid tumors. Aims: To categorize WDT-UMP using combined nuclear morphometry and immunohistochemistry of CD56, P63, and CK19. Subjects and Methods: We used CD56, P63, and CK19 immunostaining and mean nuclear area and perimeter morphometry on 20 cases of WDT-UMP, 25 cases malignant thyroid tumors, and 25 cases benign thyroid lesions. Statistical Analysis Used: Student's t-test (Unpaired), analysis of variance (ANOVA) test, and Chi-square tests by SPSS V. 20. Results: Significant differences were obtained between WDT-UMP and benign group according to the three markers, but no significant difference between WDT-UMP and malignant group. The mean nuclear area and mean nuclear perimeter were significantly higher in WDT-UMP group in comparison with the benign group while there were no significant differences with the malignant group. Conclusion: WDT-UMP are intermediate lesions differing from benign lesions of the thyroid and sharing some criteria with PTC to a certain extent.