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WHO Classification of Skin Tumors, fifth edition (2023) has newly described primary cutaneous NUT carcinoma; however, information on this cancer type remains scarce. Herein, we performed clinicopathologic and genetic analyses of 4 cases. Four elderly women (median age 77 y, range: 68 to 82 y) were included. The median tumor size was 12.5 (10 to 40 mm). Tumors were located on the scalp, temple, thigh, and palm. Two (50%) patients presented with regional lymph node metastases. Neither distant metastasis nor mortality was observed during patient follow-up of 10.5 (3 to 15) months. Sanger, panel DNA and whole-exome RNA sequencing revealed BRD3::NUTM1 (n=2) and BRD4::NUTM1 (n=2) fusions. Histology of BRD3 -rearranged tumors revealed an epidermal connection, relatively small tumor nests, and ductal or intracytoplasmic luminal formation, whereas that of BRD4 -rearranged tumors revealed large solid nests comprising discohesive tumor cells. NUT, cytokeratins, p63, EMA, TRPS1, c-MYB, CD56, and INSM1 were immunoexpressed to varying degrees in all (100%) tumors. Furthermore, diffuse SOX10 expression was common (3/4, 75%). The literature review of five previously described cases revealed women predominance, no recurrence, frequent BRD3::NUTM1 fusions, and histology of ductoglandular structures. Our study findings and literature suggest elderly women predominance, relatively frequent BRD3::NUTM1 fusions, histopathologic ductoglandular differentiation, absence of abrupt keratinisation, and a characteristic immunoprofile in primary cutaneous NUT carcinoma, unlike in that of other organ. No distant metastasis or disease-associated mortality was seen in all cases with limited follow-up., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: We investigated the efficacy of metastatic lesion radiotherapy (MLRT) in patients with metastatic nasopharyngeal carcinoma (mNPC)., Materials and Methods: Patients with mNPC from three institutions were included in this study. Propensity score matching (PSM) was employed to ensure comparability between patient groups. Overall survival (OS) rates were assessed using the Kaplan-Meier method and compared using the log-rank test. Prognostic factors were identified using univariate and multivariate Cox hazard analyses. Subgroup analyses were conducted to assess the effects of MLRT on specific patient populations., Results: We analyzed data from 1157 patients with mNPC. Patients who received MLRT had significantly better OS than those who did not, both in the original (28 vs. 21 months) and PSM cohorts (26 vs. 23 months). MLRT was identified as an independent favorable predictor of OS in multivariate analyses, with hazard ratios of 0.67. The subgroup analysis results indicated that radiotherapy effectively treated liver, lung, and bone metastatic lesions, particularly in patients with a limited tumor burden. Higher total radiation doses of MLRT (biologically effective dose (BED) ≥ 56 Gy) were associated with improved OS, while neither radiation technique nor dose fractionation independently influenced prognosis., Conclusions: MLRT offers survival advantages to patients diagnosed with mNPC. Patients with limited metastatic burden derive the most benefit from MLRT, and the recommended regimen for MLRT is a minimum BED of 56 Gy for optimal outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Purpose: Whether concurrent chemoradiotherapy would provide survival benefits in patients with stage II and T3N0 NPC with adverse factors remains unclear in IMRT era. We aimed to assess the value of concurrent chemotherapy compared to IMRT alone in stage II and T3N0 NPC with adverse features., Materials and Methods: 287 patients with stage II and T3N0 NPC with adverse factors were retrospectively analyzed, including 98 patients who received IMRT alone (IMRT alone group) and 189 patients who received cisplatin-based concurrent chemotherapy (CCRT group). The possible prognostic factors were balanced using propensity score matching (PSM). Kaplan-Meier analysis was used to evaluate the survival rates, and log-rank tests were employed to compare differences between groups., Results: The median follow-up duration was 90.8 months (interquartile range = 75.6-114.7 months). The IMRT alone and the CCRT group were well matched; however, for all survival-related endpoints, there were no significant differences between them (5-year failure-free survival: 84.3% vs. 82.7%, P value = 0.68; 5-year overall survival: 87.3% vs. 90.6%, P value = 0.11; 5-year distant metastasis-free survival: 92.8% vs. 92.5%, P value = 0.97; 5-year locoregional relapse-free survival: 93.4% vs. 89.9%, P value = 0.30). The incidence of acute toxicities in the IMRT alone group was significantly lower than that in the CCRT group., Conclusion: For patients with stage II and T3N0 NPC with adverse features treated using IMRT, no improvement in survival was gained by adding concurrent chemotherapy; however, the occurrence of acute toxicities increased significantly. For those combined with non-single adverse factors, the comprehensive treatment strategy needs further exploration., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The clinical significance of the combination of neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) is unclear. This study investigated the predictive value of pretreatment NLR (pre-NLR) combined with pretreatment PLR (pre-PLR) for the survival and prognosis of nasopharyngeal carcinoma (NPC). A total of 765 patients with non-metastatic NPC from two hospitals were retrospectively analyzed. The pre-NLR-PLR groups were as follows: HRG, high pre-NLR and high pre-PLR. MRG, high pre-NLR and low pre-PLR or low pre-NLR and high pre-PLR. LRG, neither high pre-NLR nor high pre-PLR. Receiver operating characteristic (ROC) curves were used to identify the cutoff-value and discriminant performance of the model. We compared survival rates and factors affecting the prognosis among different groups. The 5-year overall survival (OS), local regional recurrence-free survival (LRRFS) and distant metastasis-free survival (DMFS) of NPC patients in HRG were significantly poorer than those in MRG and LRG. The pre-NLR-PLR score was positively correlated with T stage, clinical stage, ECOG, and pathological classification. Multivariate cox regression analysis showed that pre-NLR-PLR scoring system, ECOG, pre-ALB, pre-CRP and pre-LMR were independent risk factors affecting 5-year OS, LRRFS and DMFS. The ROC curve showed that area under the curve (AUC) values of pre-NLR-PLR of 5-year OS, LRRFS and DMFS were higher than those of pre-NLR and pre-PLR. pre-NLR-PLR is an independent risk factor for the prognosis of NPC. The pre-NLR-PLR scoring system can be used as an individualized clinical assessment tool to predict the prognosis of patients with non-metastatic NPC more accurately and easily., (© 2024. The Author(s).)

Introduction: Acute intestinal obstruction secondary to extensive peritoneal carcinomatosis is an end stage event. The role of palliative surgery in these patients is debatable in view of the anticipated severe complications and its doubtful role in achieving adequate palliation. The primary objective of our study was to evaluate the feasibility and ability of patients to resume oral nutrition after palliative surgery for acute intestinal obstruction due to peritoneal carcinomatosis. Patients and Methods: It is an observational study in which we retrospectively reviewed the data from a prospectively maintained clinical database of 40 patients. The predefined pre- and intraoperative variables were obtained. The immediate outcome variables like postoperative complications, length of hospital stay, and mortality were analyzed. The short-term outcomes at 3 months in the form of survival, ability to resume enteral nutrition were analyzed. Results: Among the 40 patients 18 were males and 22 females. Ovarian cancer was the most common primary (27.5%) in the study. Twelve patients had acute intestinal obstruction as their first presentation without any past events and 25 (62.5%) patients had been operated on previously or received adjuvant systemic treatment. The palliative surgical option was technically feasible in 37 (93.5%) patients. The median length of hospitalization for the patients who were discharged was 10 days with a range of 6-18 days. Six (15%) patients died in the postoperative period. Severe post-operative complications were seen in 9 (26.4%) patients. Among the patients (n=34) discharged 26 (76.4%) were alive at 3 months. In those who were alive, 21 (80.7%) of them were on some form of oral nutrition at 3 months. Conclusion: Palliative surgery in patients with acute intestinal obstruction secondary to peritoneal carcinomatosis is feasible with acceptable morbidity and mortality. The enteral nutrition can be restored in the majority of these patients., (Celsius.)

Objective: To identify the differences between early- (EOCRC) and late-onset colorectal cancer (LOCRC), and to evaluate the determinants of one-year all-cause mortality among advanced-stage patients., Methods: A retrospective cohort study was carried out. CRC patients ≥ 18 years old were included. Chi-Square test was applied to compare both groups. Uni- and multivariate regressions were performed to evaluate the determinants of one-year all-cause mortality in all advanced-stage patients regardless of age of onset., Results: A total of 416 patients were enrolled; 53.1 % were female. Ninety cases (21.6 %) had EOCRC and 326 (78.4 %) had LOCRC. EOCRC cases were predominantly sporadic (88.9 %). Histology of carcinoma other than adenocarcinoma (p= 0.044) and rectum tumors (p= 0.039) were more prevalent in EOCRC. LOCRC patients were more likely to have smoking history (p < 0.001) and right colon tumors (p = 0.039). Alcohol consumption history (odds ratio [OR]: 3.375, 95 %CI: 1.022-11.150) and stage IV (OR: 12.632, 95 %CI: 3.506-45.513) were associated with higher one-year all-cause mortality among advanced-stage patients, the opposite was noted with left colon tumors (OR: 0.045, 95 %CI: 0.003-0.588)., Conclusion: EOCRC was predominantly sporadic and had more cases of uncommon histological subtypes and rectal tumors. LOCRC was characterized by a higher prevalence of smoking history. Multivariate regression revealed an association between higher one-year all-cause mortality and alcohol consumption history and stage IV in advanced-stage patients. CRC exhibited differences based on age of onset. The evaluated factors associated with CRC mortality provide valuable insights for healthcare professionals, emphasizing the importance of adequate clinical assessment and early CRC diagnosis., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: LncRNA IUR has been recently identified as a key regulator of Bcr-Abl-induced tumorigenesis, while its role in gastric carcinoma (GC) is unknown. This study investigated the involvement of IUR in GC. Materials and Methods: Gene expression levels were measured by performing quantitative polymerase chain reaction. Interactions between IUR and ROCK1 were analyzed by transfection experiments. Cell invasion and migration were analyzed by Transwell assay. Results: In this study, the authors showed that IUR was downregulated in GC. A follow-up study showed that low IUR expression levels predicted poor survival. In GC tissues, ROCK1 was upregulated in GC tissues and inversely correlated with IUR. In GC cells, IUR overexpression mediated the downregulation of ROCK1. ROCK1 overexpression resulted in increased GC cell invasion and migration, while IUR overexpression played an opposite role. Conclusion: IUR is downregulated in GC and inhibits GC cell invasion and migration by downregulating ROCK1.

Background: Human epidermal growth factor receptor 2 (HER2)-positive tumors are defined by protein overexpression (3+) or gene amplification using immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH), respectively. HER2-positive tumors have historically included both IHC(3+) and IHC(2+, equivocal)/FISH(+) tumors and received the same treatment. Differences in biology between these two tumor types, however, are poorly understood. Considering anti-HER2 drugs bind directly to HER2 protein on the cell surface, we hypothesized anti-HER2 therapies would be less effective in IHC(2+)/FISH(+) tumors than in IHC(3+) tumors, leading to differences in patient outcomes., Methods: A total of 447 patients with HER2-positive invasive carcinoma who underwent curative surgery were retrospectively investigated. HER2 status was assessed in surgical specimens, except in patients who received neo-adjuvant chemotherapy, where biopsy specimens were employed., Results: Age, tumor size, lymph node status and ER status were independent factors relating to disease-free-survival, but no difference was observed between IHC(3+) and IHC(2+)/FISH(+) tumors. Kaplan-Meier analysis found patient outcomes did not differ, even after stratifying into those that did (n = 314), or did not (n = 129), receive chemotherapy with anti-HER2 drugs. In 134 patients who received NAC, pathological complete response rates in IHC(3+) and IHC(2+)/FISH(+) tumors were 45% and 21%, respectively. Survival after developing metastasis was significantly shorter in the IHC(2+)/FISH(+) group., Conclusions: The prognosis of patients with IHC(2+)/FISH(+) tumors did not differ from IHC(3+) tumors. However, the significance of HER2 protein overexpression in relation to treatment response remains unclear and warrants further investigations., (© 2022. The Author(s).)

Background: Skin- and nipple-sparing mastectomies (SSMs/NSMs) present as an alternative for patients requiring mastectomy, with better aesthetic results. We aimed to evaluate the locoregional recurrence (LRR) rate and its predictive factors., Methods: Retrospective analysis of all consecutive cases of SSM and NSM for a primary diagnosis of in situ or invasive breast cancer, at a national cancer center, from January 1st, 2013 to May 31st, 2019. The primary outcome was LRR. Secondary outcomes included LRR predictive factors, overall survival (OS), and disease-free survival (DFS)., Results: There were included 461 patients; 402 (87%) with invasive carcinoma. The median age was 46 (interquartile range [IQR]: 40-53) years. Ninety (20%) patients had locally advanced disease. LRR rate was 3.0%, with a median follow-up time of 39 (IQR: 21-59) months. The median time to recurrence was 22 (IQR: 10-45) months. Factors independently associated with LRR were high histological grade, negative estrogen receptor status, and high Ki67 (p < 0.05). OS was 94.8% and DFS was 92.8%. LRR was associated with decreased OS., Discussion: SSM and NSM present as a safe approach to breast cancer requiring mastectomy, including selected patients with a locally advanced tumor. The associated LRR rate is 3.0%, with risk factors being high grade, negative estrogen receptor status, and high Ki67., (© 2021 Wiley Periodicals LLC.)

Background: Preoperative diagnosis for suspected gallbladder cancers is challenging, with a risk of overtreating benign disease, for example, xanthogranulomatous cholecystitis, with radical cholecystectomies. We retrospectively evaluated the surgeon's intraoperative assessment alone, and with the addition of intraoperative frozen sections, for suspected gallbladder cancers from a tertiary hepatobiliary multidisciplinary team (MDT)., Methods: MDT patients with complex gallbladder disease were included. Collated data included demographics, MDT discussion, operative details, and patient outcomes., Results: A total of 454 patients with complex gallbladder disease were reviewed, 48 (10.6%) were offered radical surgery for suspected cancer. Twenty-five underwent frozen section that led to radical surgery in 6 (25%). All frozen sections were congruent with final histopathology but doubled the operating time (p < 0.0001). Both the surgeon's subjective and additional frozen section's objective assessment, allowed for de-escalation of unnecessary radical surgery, comparing favourably to a 13.0% cancer diagnosis among radical surgery historically., Conclusions: The MDT process was highly sensitive in identifying gallbladder cancers but lacked specificity. The surgeon's intraoperative assessment is paramount in suspected cancers, and deescalated unnecessary radical surgery. Intraoperative frozen section was a safe and viable adjunct at a cost of resources and operative time., (© 2021 The Authors. Journal of Surgical Oncology published by Wiley Periodicals LLC.)

Background/aim: This study aimed to clarify the impact of proton pump inhibitors (PPIs) on oncological outcomes in patients who received pembrolizumab for advanced urothelial carcinoma (UC)., Patients and Methods: Forty advanced UC patients treated with pembrolizumab were retrospectively reviewed and divided into two groups (PPI: 15 patients; without PPI: 25 patients). Tumor response and survival were compared between these groups. The factors associated with survival were also investigated., Results: The objective response rate was significantly lower in the group with PPIs compared with the group without PPIs. Both progression-free survival (PFS) and overall survival (OS) were significantly shorter in the group with PPIs than in the group without PPIs. The use of PPIs was a significant predictor of poor PFS and OS in multivariate analysis., Conclusion: The use of PPIs was negatively associated with tumor response and survival in patients with advanced UC treated with pembrolizumab., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The optimal timing of switching from platinum-based chemotherapy to pembrolizumab in patients with advanced urothelial carcinoma (UC) remains unclear., Patients and Methods: Thirty-four patients who received pembrolizumab as second-line treatment after first-line platinum-based chemotherapy were retrospectively evaluated., Results: According to overall survival (OS) from pembrolizumab, there was a significant difference between ≤4 and >4 prior chemotherapy cycles (7.0 and 25.5 months, p=0.034), but not between ≤6 and >6 cycles (11.3 and 6.6 months, p=0.658). According to the Cox proportional hazards regression model, the number of chemotherapy cycles was not correlated with better OS in pembrolizumab-treated patients. According to the OS from the first-line treatment, there was a significant difference between ≤4 and >4 prior chemotherapy cycles (17.3 and 37.1 months, p<0.001), but not between ≤6 and >6 cycles (18.6 and 27.3 months, p=0.276)., Conclusion: The optimal timing of switching from platinum-base chemotherapy to pembrolizumab in advanced UC is around six cycles., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Despite significant increase in COVID-19 publications, characterization of COVID-19 infection in patients with gynecologic cancer remains limited. Here we present an update of COVID-19 outcomes among people with gynecologic cancer in New York City (NYC) during the initial surge of severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019 [COVID-19])., Methods: Data were abstracted from gynecologic oncology patients with COVID-19 infection among 8 NYC area hospital systems between March and June 2020. Multivariable logistic regression was utilized to estimate associations between factors and COVID-19 related hospitalization and mortality., Results: Of 193 patients with gynecologic cancer and COVID-19, the median age at diagnosis was 65.0 years (interquartile range (IQR), 53.0-73.0 years). One hundred six of the 193 patients (54.9%) required hospitalization; among the hospitalized patients, 13 (12.3%) required invasive mechanical ventilation, 39 (36.8%) required ICU admission. Half of the cohort (49.2%) had not received anti-cancer treatment prior to COVID-19 diagnosis. No patients requiring mechanical ventilation survived. Thirty-four of 193 (17.6%) patients died of COVID-19 complications. In multivariable analysis, hospitalization was associated with an age ≥ 65 years (odds ratio [OR] 2.12, 95% confidence interval [CI] 1.11, 4.07), Black race (OR 2.53, CI 1.24, 5.32), performance status ≥2 (OR 3.67, CI 1.25, 13.55) and ≥ 3 comorbidities (OR 2.00, CI 1.05, 3.84). Only former or current history of smoking (OR 2.75, CI 1.21, 6.22) was associated with death due to COVID-19 in multivariable analysis. Administration of cytotoxic chemotherapy within 90 days of COVID-19 diagnosis was not predictive of COVID-19 hospitalization (OR 0.83, CI 0.41, 1.68) or mortality (OR 1.56, CI 0.67, 3.53)., Conclusions: The case fatality rate among patients with gynecologic malignancy with COVID-19 infection was 17.6%. Cancer-directed therapy was not associated with an increased risk of mortality related to COVID-19 infection., Competing Interests: Declaration of Competing Interest B.P. reports grants, personal fees and non-financial support outside the submitted work; institutional PI for industry sponsored trials from Tesaro/GSK, AstraZeneca, Merck, Genentech/ Roche, Celison, Mersana and Clovis Oncology. Compensated advisory boards include Tesaro/GSK, AstraZeneca, Merck, Elevar, Arquer, Toray, and Eisai. J.J. reports a patent license from MDSeq Inc. R.OC reports personal fees from Tesaro, GlaxoSmithKline, Regeneron, Seagen, Fresenius Kabi, Genentech USA and Gynecologic Oncology Foundation, outside the submitted work and non-compensated steering committee member for the PRIMA, Moonstone (Tesaro/GSK) and DUO-O (AstraZeneca) studies. R.OC's institute receives funding for clinical research from Bayer/Celgene/Juno, Tesaro/GSK, Ludwig Cancer Institute, Abbvie/StemCentrx, Regeneron, TCR2 Therapeutics, Atara Biotherapeutics, Marker Therapeutics, Syndax Pharmaceuticals, Genmab/Seagen Therapeutics, Sellas Therapeutics, Genentech, Kite Pharma, Gynecologic Oncology Foundation. S.V.B. has research collaborations with Roche/Genentech, Tesaro/GK, Seattle Genetics, Merck and Asta Zeneca, from which her institution receives funding., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: As a common head and neck tumor, laryngeal cancer has attracted heightened attention for its treatment and prognosis. Surgery and radiotherapy were mainly therapeutic approaches in laryngeal cancer, and intensity-modulated radiotherapy (IMRT) was a precision treatment way in radiotherapy. However, the therapeutic effect of surgery plus IMRT in laryngeal cancer was rarely reported. This study aims to determine the effect of IMRT on the treatment of patients with laryngeal cancer., Methods: A total of 125 patients with laryngeal cancer were collected and retrospectively analyzed based on their clinical data and follow-up results. These patients had a clear treatment plan for surgery and intensity-modulated radiotherapy., Results: Smoking, lymph node metastasis, TNM staging and therapeutic approaches could affect the survival of patients with laryngeal cancer. It was shown that the laryngeal function retention rate in the simple IMRT group was significantly higher than the simple surgery group and surgery plus IMRT group. The 5-year survival rate of surgery plus IMRT, simple surgery and simple IMRT were 82.86%, 53.85% and 43.33%, respectively. The locoregional recurrences rate of surgery plus IMRT, simple surgery and simple IMRT were 14.29%, 34.62% and 43.33%., Conclusion: Surgery plus IMRT was a feasible and efficacious treatment technique for patients with laryngeal cancer, which effectively prolong the survival time of patients., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background/aim: The efficacy of programmed cell death 1 (PD-1) inhibitor therapy for patients with recurrent and/or metastatic salivary gland carcinoma (R/M SGC) remains unclear., Patients and Methods: We retrospectively analyzed 36 patients with R/M SGC treated with PD-1 inhibitor. The expression of programmed cell death ligand 1 (PD-L1) and mismatch repair (MMR) proteins was also analyzed., Results: The objective response rate (ORR) was 11.1%. The histopathological subtypes of patients who achieved complete response or partial response were salivary duct carcinoma (SDC) in three patients and poorly differentiated carcinoma in one patient, all of whom showed a positive PD-L1 expression. The expression of MMR proteins was not associated with the efficacy of PD-1 inhibitors., Conclusion: Although the efficacy of PD-1 inhibitor therapy in R/M SGC is limited, certain patients may respond and achieve long-term disease control. There is a potential therapeutic effect in SDC patients with positive PD-L1 expression., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The phase III MAX clinical trial randomised patients with metastatic colorectal cancer (mCRC) to receive first-line capecitabine chemotherapy alone or in combination with the anti-VEGF-A antibody bevacizumab (± mitomycin C). We utilised this cohort to examine whether single nucleotide polymorphisms (SNPs) in VEGF-A, VEGFR1, and VEGFR2 are predictive of efficacy outcomes with bevacizumab or the development of hypertension. Genomic DNA extracted from archival FFPE tissue for 325 patients (69% of the MAX trial population) was used to genotype 16 candidate SNPs in VEGF-A, VEGFR1, and VEGFR2, which were analysed for associations with efficacy outcomes and hypertension. The VEGF-A rs25648 'CC' genotype was prognostic for improved PFS (HR 0.65, 95% CI 0.49 to 0.85; P = 0.002) and OS (HR 0.70, 95% CI 0.52 to 0.94; P = 0.019). The VEGF-A rs699947 'AA' genotype was prognostic for shorter PFS (HR 1.32, 95% CI 1.002 to 1.74; P = 0.048). None of the analysed SNPs were predictive of bevacizumab efficacy outcomes. VEGFR2 rs11133360 'TT' was associated with a lower risk of grade ≥ 3 hypertension (P = 0.028). SNPs in VEGF-A, VEGFR1 and VEGFR2 did not predict bevacizumab benefit. However, VEGF-A rs25648 and rs699947 were identified as novel prognostic biomarkers and VEGFR2 rs11133360 was associated with less grade ≥ 3 hypertension., (© 2022. The Author(s).)

The significance of N 6 -methyladenosine (m6A) RNA modifications in the progression of breast cancer (BC) has been recognised. However, their potential role and mechanism of action in the tumour microenvironment (TME) and immune response has not been demonstrated. Thus, the role of m6A regulators and their downstream target gene components in BC remain to be explored. In this study, we used a series of bioinformatics methods and experiments to conduct exploratory research on the possible role of m6A regulators in BC. First, two regulatory modes of immune activation and inactivation were determined by tumour classification. The TME, immune cell infiltration, and gene set variation analysis results confirmed the reliability of this pattern. The prognostic model of the m6A regulator was established by the least absolute shrinkage and selection operator and univariate and multivariate Cox analyses, with the two regulators most closely related to survival verified by real-time quantitative reverse transcription polymerase chain reaction. Next, the prognostic m6A regulator identified in the model was crossed with the differential copy number of variant genes in invasive BC (IBC), and it was determined that YTHDF1 was a hub regulator. Subsequently, single-cell analysis revealed the expression patterns of m6A regulators in different IBC cell populations and found that YTHDF1 had significantly higher expression in immune-related IBC cells. Therefore, we selected the intersection of the BC differential expression gene set and the differential expression gene set of a cell line with knocked-down YTHDF1 in literature to identify downstream target genes of YTHDF1, in which we found IFI6, EIR, and SPTBN1. A polymerase chain reaction was conducted to verify the results. Finally, we confirmed the role of YTHDF1 as a potential prognostic biomarker through pan-cancer analysis. Furthermore, our findings revealed that YTHDF1 can serve as a new molecular marker for BC immunotherapy., (© 2022. The Author(s).)

Individual cell types of human tissues have their own CpG site methylation profiles, which might be utilized for the development of methylation markers to denote tumor-infiltrating lymphocytes (TILs). We aimed to develop DNA methylation markers that recapitulate the densities of TILs in gastric carcinoma (GC). Through genome-wide methylation profiling, NCOR2, PARK2, and ZSCAN12 were found to be highly methylated in CD3-positive and CD8-positive cells and rarely methylated in tumor cells. Scores of the three methylation markers were analyzed for their relationship with the overall survival and recurrence-free survival of patients with advanced GC (n = 471). The scores of three methylation markers were closely associated with densities of CD3-positive or CD8-positive cells at the tumor center or invasive front of GCs and found to be a significant prognostic factor in univariate analysis of overall survival and recurrence-free survival. In multivariate analysis, the highest score showed hazard ratios of 0.513 (CI 0.306-0.857) and 0.434 (CI 0.261-0.720) for overall survival and recurrence-free survival, respectively. The findings suggest that methylation markers signifying TILs might be utilized for the recapitulation of TIL density in GCs and serve as biomarkers for predicting prognosis in patients with GC., (© 2022. The Author(s).)

Background: According to 2018 ASCO/CAP guideline, HER2 FISH-equivocal breast cancers will be categorized as HER2 negative except those with IHC 3+. However, whether or not HER2 FISH-equivocal breast cancers was a heterogeneous group has not been well illustrated., Methods: 195 HER2 FISH-equivocal breast cancer samples were collected from 2014 to 2018. The molecular subtype was identified according to 2013 St Gallen consensus, and HER2 status was also re-determined following 2018 ASCO/CAP guideline. All samples were classified into 4 groups according to the average HER2 copy number (4.0-4.4, 4.5-4.9, 5.0-5.4, 5.5-5.9 signals/cell). The relationship between HER2 copy number and clinicopathological parameters was analyzed., Results: 183 (93.8%) of 195 FISH-equivocal cases were classified as luminal-like subtype, while the other 12 (6.2%) were undetermined. Following 2018 ASCO/CAP guideline, all FISH-equivocal cases were recategorized as HER2 negative. Therefore, 31(15.9%) cases were luminal A-like, 152 (77.9%) were luminal B-like (HER2 negative) and 12 (6.2%) were triple negative. The average HER2 copy number showed a positive correlation with chromosome 17 polysomy, but had no significant association with other clinicopathological parameters as well as prognosis. 17 (8.7%) patients were treated with trastuzumab, but showed no difference in prognosis with those who didn't receive targeted therapy., Conclusions: In this study, all HER2 FISH-equivocal breast cancers were recategorized as HER2 negative according to 2018 ASCO/CAP guideline. Most of these patients were luminal B-like (HER2 negative). The average HER2 copy number had no significant association with clinicopathological parameters, as well as prognosis., (© 2021. The Author(s).)

Background: Breast cancer is one of the most common types of cancer. Ribonucleotide reductase (RNR) is a heterodimeric tetramer consisting of two Ribonucleoside-diphosphate reductase large subunits (RRM1) and two Ribonucleoside-diphosphate reductase small subunits (RRM2). RRM2 is the building subunit of RNR that is important for synthesis of Deoxynucleoside triphosphate (dNTP) during S phase of cell cycle during DNA replication. RRM2 is associated with poor prognosis in lung and colorectal cancer. In breast cancer, increased RRM2 protein level is strongly correlated with large tumour size, positive lymph node and relapse. In this study, we aimed to study expression of RRM2 in breast cancer and to correlate it with different clinicopathological parameters in Egyptian women., Material and Methods: This study was performed by investigating RRM2 protein expression in breast cancer and correlating the results with other clinicopathological variables using immunohistochemistry and tissue microarrays., Results: About 77% of cases were RRM2 positive. High Ki67 was observed in cases with high RRM2 score. The majority of non-luminal cases expressed RRM2, however this was statistically insignificant. In ER positive group, RRM2 expression was associated with shorter disease free survival with borderline significance., Conclusion: RRM2 protein expression can help in evaluating outcome of breast cancer patients and could be a potential therapeutic target., (© 2021. The Author(s).)

Background: New evidence from clinical and fundamental researches suggests that SNHG7 is involved in the occurrence and development of carcinomas. And the increased levels of SNHG7 are associated with poor prognosis in various kinds of tumors. However, the small sample size was the limitation for the prognostic value of SNHG7 in clinical application. The aim of the present meta-analysis was to conduct a qualitative analysis to explore the prognostic value of SNHG7 in various cancers., Methods: Articles related to the SNHG7 as a prognostic biomarker for cancer patients, were comprehensive searched in several electronic databases. The enrolled articles were qualified via the preferred reporting items for systematic reviews and meta-analysis of observational studies in epidemiology checklists. Additionally, an online database based on The Cancer Genome Atlas (TCGA) was further used to validate our results., Results: We analyzed 2418 cancer patients that met the specified criteria. The present research indicated that an elevated SNHG7 expression level was significantly associated with unfavorable overall survival (OS) (HR = 2.45, 95% CI: 2.12-2.85, p <0.001). Subgroup analysis showed that high expression levels of SNHG7 were also significantly associated with unfavorable OS in digestive system cancer (HR = 2.31, 95% CI: 1.90-2.80, p <0.001) and non-digestive system cancer (HR = 2.67, 95% CI: 2.12-3.37, p <0.001). Additionally, increased SNHG7 expression was found to be associated with tumor stage and progression (III/IV vs. I/II: HR = 1.76, 95% CI: 1.57-1.98, p <0.001). Furthermore, elevated SNHG7 expression significantly predicted lymph node metastasis (LNM) (HR = 1.98, 95% CI: 1.74-2.26, p <0.001) and distant metastasis (DM) (HR = 2.49, 95% CI: 1.88-3.30, p <0.001) respectively. No significant heterogeneity was observed among these studies. SNHG7 was significantly upregulated in four cancers and the elevated expression of SNHG7 predicted shorter OS in four cancers, worse DFS in five malignancies and worse PFI in five carcinomas based on the validation using the GEPIA on-line analysis tool., Conclusions: The present analysis suggests that elevated SNHG7 is significantly associated with unfavorable OS, tumor progression, LNM and DM in various carcinomas, and may be served as a promising biomarker to guide therapy for cancer patients., (© 2021. The Author(s).)

Low-grade neuroendocrine carcinoma of the skin (LGNECS) was proposed in 2017 as a new primary cutaneous neoplasm with neuroendocrine differentiation; however, it is not yet well known due to its rarity. Herein, we perform a detailed clinicopathologic analysis of 13 cases as well as panel DNA sequencing in three cases. The study included 12 males and 1 female with a median age of 71 (43-85) years. All lesions occurred on the ventral trunk. The mean tumor size was 2.2 (0.8-11.0) cm. The histopathology resembled that of well-differentiated neuroendocrine tumors (NETs) in other organs, but intraepidermal pagetoid spreading was seen in 8 (61.5%) cases and stromal mucin deposits in 4 (30.8%). Immunoreactivity for CK7, CK19, EMA, BerEP4, CEA, chromogranin A, synaptophysin, INSM1, GCDFP15, GATA3, ER, and bcl-2 were present in varying degrees in all tested cases. PTEN c.165-1G>A splice site mutation was detected by panel sequencing in one case, and GATA3 P409fs*99 and SETD2 R1708fs*4 in another case. Lymph node metastasis was seen significantly in cases with tumor size >2.0 cm [8/8 (100%) vs. 1/5 (20%)]. All three cases with size >3.0 cm were in unresectable advanced-stage [3/3 (100%) vs. 1/10 (10%)], and two of the three patients succumbed to the disease. The two cases of death revealed mild nuclear atypia (mitosis: 1/10 HPFs) and moderate nuclear atypia (2/10 HPFs). Thus, tumor size would be a better prognostic factor than nuclear atypia, mitotic count, and Ki67 index, unlike in NETs. These clinicopathologic and immunohistochemical features would represent the characteristics as skin adnexal tumors with apocrine/eccrine differentiation rather than NETs; therefore, we rename it as sweat-gland carcinoma with neuroendocrine differentiation (SCAND)., (© 2021. The Author(s), under exclusive licence to United States & Canadian Academy of Pathology.)

The development of somatic-type malignancies (SMs) in testicular germ cell tumors (GCTs) is a rare but well-recognized phenomenon. We studied the pathologic features of 63 GCTs with SMs in the testis (n=22) or metastases (n=41) and correlated these features with clinical outcomes. The patients with SMs in the testis (median age, 26 y) were younger than those with metastatic SMs (median age, 38.5 y). The SMs consisted of carcinomas (n=21), sarcomas (n=21), primitive neuroectodermal tumors (n=15), nephroblastomas (n=3), and mixed tumors (n=3). Sarcoma was the most common SM in the testis (n=11), and most sarcomas were rhabdomyosarcomas (n=9). Carcinoma was the most common SM in metastases (n=20), and most carcinomas were adenocarcinomas (n=12). In metastases, carcinomatous SMs developed after a longer interval from the initial orchiectomy (median times, 213 mo) than sarcomatous SMs (median times, 68 mo). Patients with metastatic SMs had significantly poorer overall survival than those with SMs in the testis (5-y survival rate, 35% vs. 87%; P=0.011). Furthermore, patients with carcinomatous SMs had a significantly worse prognosis than those with sarcomatous or primitive neuroectodermal tumor SMs (5-y survival rates, 17%, 77%, and 73%, respectively; P=0.002), when the whole cohort, including testicular and metastatic SMs, were analyzed. Our results demonstrate that SMs in metastatic GCTs are associated with a significantly worse prognosis than those in the testis. Furthermore, the histologic subtype of SM has a significant effect on the clinical outcome, with the carcinomatous SM carrying the highest risk for mortality., Competing Interests: Conflicts of Interest and Source of Funding: Supported by the NIH/NCI under award number P30CA016672. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Uterine corpus endometrial carcinoma (UCEC) is a gynecological malignant tumor with low survival rate and poor prognosis. The traditional clinicopathological staging is insufficient to estimate the prognosis of UCEC. It is necessary to select a more effective prognostic signature of UCEC to predict the prognosis and immunotherapy effect of UCEC., Methods: CIBERSORT and weighted correlation network analysis (WGCNA) algorithms were combined to screen modules related to regulatory T (Treg) cells. Subsequently, univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses were used to identify the genes in key modules. The difference in overall survival (OS) between high- and low-risk patients was analyzed by Kaplan-Meier analysis. The Tregs-related risk signature (TRRS) was screened by uni- and multivariate Cox analyses. Afterward, we analyzed the expression difference of TRRS and verified its ability to predict the prognosis of UCEC and the effect of immunotherapy., Results: Red module has the highest correlation with Tregs among all clustered modules. Pathways enrichment indicated that the related processes of UCEC were primarily associated to the immune system. Eight genes (ZSWIM1, NPRL3, GOLGA7, ST6GALNAC4, CDC16, ITPK1, PCSK4, and CORO1B) were selected to construct TRRS. We found that this TRRS is a significantly independent prognostic factor of UCEC. Low-risk patients have higher overall survival than high-risk patients. The immune status of different groups was different, and tumor-related pathways were enriched in patients with higher risk score. Low-risk patients are more likely take higher tumor mutation burden (TMB). Meanwhile, they are more sensitive to chemotherapy than patients with high-risk score, which indicated a superior prognosis. Immune checkpoints such as PD-1, CTLA4, PD-L1, and PD-L2 all had a higher expression level in low-risk group. TRRS expression really has a relevance with the sensitivity of UCEC patients to chemotherapeutic drugs., Conclusion: We developed and validated a TRRS to estimate the prognosis and reflect the immune status of UCEC, which could accurately assess the prognosis of patients with UCEC and supply personalized treatments for them., 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 © 2021 Liu, Geng, Yang, Shao, Zhong, Yang, Ni, Cai and Bai.)

Background: The lncRNA BACE1-AS was identified as a plasma molecular marker in the early diagnosis of Alzheimer's disease, but its role in tumors remains poorly defined., Methods: The expression patterns, genomic mutation, and prognostic significance of BACE1-AS in pan-cancers were compared by analyzing 32 types of tumors from The Cancer Genome Atlas and cBioPortal databases. The relationships between BACE1-AS expression levels and the degree of immune cell infiltration, immune components, and immune-related genes were explored. The possible molecular mechanisms of BACE1-AS in tumors were explored using gene set enrichment analysis (GSEA). Finally, the role of BACE1-AS in hepatocellular carcinoma was confirmed via quantitative real-time polymerase chain reaction (qRT-PCR)., Results: BACE1-AS expression levels were significantly upregulated in LIHC, GBM, KIRC, CHOL, STAD, KICH, COAD, and PRAD. Higher expression levels of BACE1-AS were associated with worse overall survival in patients with HNSC and LIHC, while the opposite was found in PCPG and THCA. The overall mutation rate of BACE1-AS in pan-cancer was only approximately 0.9%, and it occurred mainly in uveal melanoma and uterine carcinoma. Generally, BACE1-AS expression was negatively correlated with the immune microenvironment. BACE1-AS expression was mainly related to naïve B cells, activated memory CD4 T cells, monocytes, M1 macrophages, M2 macrophages, and resting mast cells. The potential mechanisms of BACE1-AS in tumors were mainly via regulating the activities of B cell-mediated immunity, immune response regulating cell surface receptor signaling, RNA binding in posttranscriptional gene silencing, B cell receptor signaling pathways, and immune receptor activity. Finally, the qRT-PCR results confirmed that the expression levels of BACE1-AS in hepatocellular carcinoma cell lines were upregulated., Conclusions: Overall, our results suggest that BACE1-AS is associated with the expression, prognosis, and rate of immune cell infiltration of most tumors. Thus, BACE1-AS may be a potential target for immunotherapies aimed at improving cancer patient outcomes., 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 © 2021 Mengmeng Wang et al.)

Objective: To compare disease-free survival between minimally invasive surgery and open surgery in patients with high-risk endometrial cancer., Methods: We conducted a multicentric, propensity-matched study of patients with high-risk endometrial cancer who underwent hysterectomy, bilateral salpingo-oophorectomy, and staging between January 1999 and June 2016 at two centers. High-risk endometrial cancer included grade 3 endometrioid, serous, clear cell, undifferentiated carcinoma or carcinosarcoma with any myometrial invasion. Patients were categorized a priori into two groups based on surgical approach, propensity scores were calculated based on potential confounders and groups were matched 1:1 using nearest neighbor technique. Cox hazard regression analysis and Kaplan-Meier curves evaluated the association of surgical technique with survival., Results: Of 626 eligible patients, 263 (42%) underwent minimally invasive surgery and 363 (58%) underwent open surgery. In the matched cohort, there were no differences in disease-free survival rates at 5 years between open (53.4% [95% CI 45.6-60.5%]) and minimally invasive surgery (54.6% [95% CI 46.6-61.8]; P=.82). Minimally invasive surgery was not associated with worse disease-free survival (hazard ratio [HR] 0.85, 95% CI 0.63-1.16; P=.30), overall survival (HR 1.04, 95% CI 0.73-1.48, P=.81), or recurrence rate (HR 0.99; 95% CI 0.69-1.44; P=.99) compared with open surgery. Use of uterine manipulator was not associated with worse disease-free survival (HR 1.01, 95% CI 0.65-1.58, P=.96), overall survival (HR 1.18, 95% CI 0.71-1.96, P=.53), or recurrence rate (HR 1.12, 95% CI 0.67-1.87; P=.66)., Conclusion: There was no difference in oncologic outcomes comparing minimally invasive and open surgery among patients with high-risk endometrial cancer., Competing Interests: Financial Disclosure The authors did not report any potential conflicts of interest., (Copyright © 2021 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Gastric cancer (GC) is one of the common digestive malignancies worldwide and causes a severe public health issue. So far, the underlying mechanisms of GC are largely unclear. Thus, we aim to identify the long non-coding RNA (lncRNA)-associated competing endogenous RNA (ceRNA) for GC., Methods: TCGA database was downloaded and used for the identification of differentially expressed (DE) lncRNAs, miRNAs, and mRNAs, respectively. Then, the ceRNA network was constructed via multiple online datasets and approaches. In addition, various in vitro assays were carried out to validate the effect of certain hub lncRNAs., Results: We constructed a ceRNA network, including 76 lncRNAs, 18 miRNAs, and 159 mRNAs, which involved multiple critical pathways. Next, univariate and multivariate analysis demonstrated 11 lncRNAs, including LINC02731, MIR99AHG, INHBA-AS1, CCDC144NL-AS1, VLDLR-AS1, LIFR-AS1, A2M-AS1, LINC01537, and LINC00702, and were associated with OS, and nine of those lncRNAs were considered as hub lncRNAs involved in the sub-ceRNA network. The in vitro assay indicated two lncRNAs, INHBA-AS1 and CCDC144NL-AS1, which were positively related to the GC aggressive features, including proliferation, invasion, and migration., Conclusions: We identified nine hub lncRNAs and the associated ceRNA network related to the prognosis of GC, and then validated two out of them as promising oncogenes in GC., (© 2021 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Background: Cervical carcinoma is one of the most common malignant tumors of the female reproductive system. Lymph nodes metastasis, the most common metastasis, which can be detected even in small-size tumor patients, results in worse prognosis. Therefore, it is of great significance to explore novel lymph nodes metastasis associated biomarkers, which can predict the prognosis and provide a good reference for clinical decision making in cervical carcinoma patients. However, systematic and comprehensive studies related to the key molecules in lymph node metastasis in cervical carcinoma patients are still absent., Methods: Transcriptome and clinical data of 307 cervical carcinoma patients were obtained from The Cancer Genome Atlas (TCGA). Then, survival of patients with and without lymph node metastasis was analyzed by Kaplan-Meier (K-M) curves. Differential expressed genes (DEGs) were detected between tumor and control samples using limma package and defined as lymph node metastasis related genes. Univariate and multivariate Cox regression analyses were carried out to screen robust prognostic gene signature. The risk score model and nomogram for predicting survival were constructed based on prognostic gene signature. The performance of the risk score model was evaluated by operating characteristic (ROC) curves. Based on risk score, patients were divided into low- and high- risk groups. DEGs, functional enrichment analysis and tumor microenvironment (immune infiltration and expressions of immune checkpoints) were detected in low- and high-risk groups., Results: A total of 103 lymph node metastasis-associated genes were identified. Univariate and multivariate Cox regression analyses identified TEKT2, LPIN2, FABP4 and CXCL2 as prognostic gene signature. The risk score model was constructed and validated in cervical carcinoma patients. 345 DEGs identified between high- and low-risk groups were significantly enriched into immune-related biological processes. Furthermore, we found that the immune infiltration and expressions of immune checkpoints were significantly different between low- and high-risk groups., Conclusion: Our study revealed that lymph node metastasis played an important role in the prognosis of cervical carcinoma patients. Furthermore, we established a risk score model based on lymph node metastasis related genes, which could accurately predict the survival of cervical carcinoma patients. Besides, our findings in tumor microenvironments of low- and high-risk groups improved our understanding of the relationship between lymph node metastasis related genes and cervical carcinoma., (© 2021. The Author(s).)

Background: Pembrolizumab has efficacy in programmed death ligand 1 (PD-L1)-positive metastatic or unresectable cervical cancer that has progressed during chemotherapy. We assessed the relative benefit of adding pembrolizumab to chemotherapy with or without bevacizumab., Methods: In a double-blind, phase 3 trial, we randomly assigned patients with persistent, recurrent, or metastatic cervical cancer in a 1:1 ratio to receive pembrolizumab (200 mg) or placebo every 3 weeks for up to 35 cycles plus platinum-based chemotherapy and, per investigator discretion, bevacizumab. The dual primary end points were progression-free survival and overall survival, each tested sequentially in patients with a PD-L1 combined positive score of 1 or more, in the intention-to-treat population, and in patients with a PD-L1 combined positive score of 10 or more. The combined positive score is defined as the number of PD-L1-staining cells divided by the total number of viable tumor cells, multiplied by 100. All results are from the protocol-specified first interim analysis., Results: In 548 patients with a PD-L1 combined positive score of 1 or more, median progression-free survival was 10.4 months in the pembrolizumab group and 8.2 months in the placebo group (hazard ratio for disease progression or death, 0.62; 95% confidence interval [CI], 0.50 to 0.77; P<0.001). In 617 patients in the intention-to-treat population, progression-free survival was 10.4 months and 8.2 months, respectively (hazard ratio, 0.65; 95% CI, 0.53 to 0.79; P<0.001). In 317 patients with a PD-L1 combined positive score of 10 or more, progression-free survival was 10.4 months and 8.1 months, respectively (hazard ratio, 0.58; 95% CI, 0.44 to 0.77; P<0.001). Overall survival at 24 months was 53.0% in the pembrolizumab group and 41.7% in the placebo group (hazard ratio for death, 0.64; 95% CI, 0.50 to 0.81; P<0.001), 50.4% and 40.4% (hazard ratio, 0.67; 95% CI, 0.54 to 0.84; P<0.001), and 54.4% and 44.6% (hazard ratio, 0.61; 95% CI, 0.44 to 0.84; P = 0.001), respectively. The most common grade 3 to 5 adverse events were anemia (30.3% in the pembrolizumab group and 26.9% in the placebo group) and neutropenia (12.4% and 9.7%, respectively)., Conclusions: Progression-free and overall survival were significantly longer with pembrolizumab than with placebo among patients with persistent, recurrent, or metastatic cervical cancer who were also receiving chemotherapy with or without bevacizumab. (Funded by Merck Sharp and Dohme; KEYNOTE-826 ClinicalTrials.gov number, NCT03635567.)., (Copyright © 2021 Massachusetts Medical Society.)

Background/aim: Systemic immune-inflammation index (SII) predicts survival of patients with various malignancies. This study explored the prognostic value of SII in metastatic urothelial carcinoma (MUC) subjects., Patients and Methods: We evaluated 181 consecutive MUC patients treated with first-line platinum-based therapy. Karnofsky performance status <80% and visceral metastasis were present in 18.2% and 46.4% of patients, respectively. SII was based on platelet × neutrophil/lymphocyte counts. Study population was dichotomized by median into high and low SII groups before the initiation of chemotherapy and at week 6. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method and compared with the log-rank test., Results: At median follow-up of 9.6 months, 174 patients experienced disease progression and 173 died. Patients with low SII at baseline and at week 6 had significantly better PFS (HR=0.58; p=0.0002 and HR=0.55; p<0.0001) and OS (HR=0.54; p<0.0001 and HR=0.54; p<0.0001) compared to patients with high SII. Independent prognostic value of SII was confirmed in a multivariate analysis., Conclusion: High SII before chemotherapy that persists at week 6 negatively affects survival. SII at baseline can be used in the stratification of patients within clinical trials and in clinical practice., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: This study aimed to investigate the response to platinum-based chemotherapy rechallenge in patients with pembrolizumab-refractory urothelial carcinoma., Patients and Methods: We retrospectively reviewed 14 patients with pembrolizumab-refractory urothelial carcinoma. Each patient received a regimen that they had not previously received (paclitaxel plus carboplatin in 10, gemcitabine plus docetaxel and carboplatin in four). Tumor response and adverse events were assessed. We evaluated overall survival from the chemotherapy rechallenge start date until death., Results: The median overall survival was 11.2 months. The disease-control rate was 85.7%. Partial responses occurred in the metastases in lymph nodes in three (37.5%) patients, lung in one (25%), peritoneal in three (75%), and liver in three (100%). Neutropenia of grade ≥3 occurred in 13 (92.9%) patients., Conclusion: The activity of platinum-based chemotherapy rechallenge after pembrolizumab was maintained. Neutropenia was observed in most patients., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objective: To analyze the prognosis of cutaneous adnexal malignancies, survival relative to surgical management, and utility of lymph-node biopsy., Design: Population-based study of the SEER-18 database from 1975 to 2016., Participants: 7591 patients with sweat gland carcinoma, hidradenocarcinoma, spiradenocarcinoma, sclerosing sweat duct tumor/microcystic adnexal tumor (SSDT/MAC), porocarcinoma, eccrine adenocarcinoma, and sebaceous carcinoma RESULTS: Five-year OS ranged from 68.0 to 82.6%, while 5-year DSS ranged from 94.6 to 99.0%. The majority of patients were treated with narrow (42.4%) or wide local excision (16.9%). DSS at 5 years showed that patients with stage IV had significantly poorer survival (50.3%) than I, II, or III (99.3%, 97.8%, and 89.0% respectively). 5-year OS was significantly higher for narrow excision (excision with < 1 cm margin, 78.5%) than observation (65.0%), excisional biopsy (66.8%), or wide local excision (WLE, 73.2%). Lymph-node biopsy was performed in a minority of cases (8.1%) and patients showed no significant difference in survival based on nodal status. The sensitivity and specificity of lymph-node biopsy for all malignancies were 46% and 80%, respectively. The PPV and NPV for that group were 0.46 and 0.80, respectively. Invasion of deep extradermal structures was a poor predictor of nodal positivity., Conclusions: These malignancies have excellent DSS. Narrow excisions demonstrate better 5-year DSS and OS compared with WLE. Lymph-node biopsy is a poor predictor of survival in advanced stage disease and utility is limited., (© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: It remains unclear whether lymph node dissection is necessary for patients with N0 gallbladder carcinoma (GBC). The objective of this study was to evaluate the effect of lymphadenectomy on the prognosis for N0 GBC patients. The secondary objective was to establish a prognostic model of survival for N0 GBC patients being founded on the large samples., Methods: Patient data were obtained from the database named SEER (Surveillance, Epidemiology, and End Results database) between 2010 and 2014. Analyses of Kaplan-Meier survival and multivariate Cox regression were performed in subgroups based on regional lymph nodes removal (LNR) to calculate the excess risk of cause-specific death. A prognosis nomogram was constructed build on the results of a multivariate analysis to predict the specific survival time (CSS) rates of N0 GBC patients., Result: A total of 1406 N0 GBC patients were included in this research. The majority of N0 GBC patients undergoing cancer-directed surgery did not undergo LNR (64.5%). The results showed that LNR can improve the survival of N0 GBC patients, including those at the T1a and T1b stages, and a wider range of lymph node dissection (LNR2) compared to LNR1 was more conducive to the prognosis. Furthermore, multivariate regression analysis showed that LNR was an independent favorable prognostic factor of N0 GBC. Finally, a nomogram was constructed to accurately predict the prognosis of N0 gallbladder cancer patients., Conclusion: This study demonstrated a significant survival benefit for extended lymph nodes removed in N0 GBC patients. These results recommend that an extended lymph node dissection strategy is needed for N0 GBC patients., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: To assess the effect of race/ethnicity in cancer-specific mortality (CSM) adjusted for other-cause mortality (OCM) in metastatic prostate cancer patients (mPCa) treated with external beam radiotherapy (EBRT) to the prostate., Methods: We relied on the Surveillance, Epidemiology, and End Results (SEER) database to identify Caucasian, African-American, Hispanic/Latino and Asian mPCa patients treated by EBRT between 2004 and 2016. Cumulative incidence plots displayed CSM after adjustment for OCM according to race/ethnicity. Propensity score matching accounted for patient age, prostate-specific antigen, clinical T and N stages, Gleason Grade Groups and M1 substages. OCM adjusted multivariable analyses tested for differences in CSM in African-Americans, Hispanic/Latinos and Asians relative to Cauacasians., Results: After 3:1 propensity score matching and OCM adjustment, Asians exhibited lower CSM at 60 and 120 months (48.2 and 60.0%, respectively) compared to Caucasians (66.7 and 79.4%, respectively, p < 0.001). In OCM adjusted multivariable analyses, Asian race/ethnicity was associated with lower CSM (HR 0.66, CI 0.52-0.83, p < 0.001). Conversely, African-American and Hispanic/Latino race/ethnicity did not affect CSM. OCM rates were comparable between examined races/ethnicities., Conclusion: In the setting of mPCa treated with EBRT, Asians exhibit lower CSM than Caucasians, African-Americans and Hispanic/Latinos. This observation may warrant consideration in prognostic stratification schemes for newly diagnosed mPCa patients., (© 2021. The Author(s).)

Objective: Glottic cancer has an excellent probability of cure. The early glottic cancer is usually treated by radiotherapy with different fractionation schedules. The aim of this study was to compare conventional versus hypofractionated radiotherapy with respect to overall survival and disease-free survival., Materials and Methods: A total of fifty patients with T1-2N0M0 glottic cancer with no previous treatment history were prospectively randomized into two arms. In Arm A (Study), patients received a total of 55 Gy in 20# at 2.75 Gy/#, 5 days a week. In Arm B (Control), patients received a total of 66 Gy in 33# at 2 Gy/#, 5 days a week. Disease response was evaluated by the WHO criteria at the end of treatment, then at 1, 2, and 3 months to complete their 6-month follow-up. Overall survival and disease-free survival were evaluated at 1, 2, and 3 years., Results: Overall, 100% of patients in the study arm and 96% of patients in the control arm had complete response after 6 months. Overall survival rates at 1, 2, and 3 years were 96%, 96%, and 88%, respectively, in the study arm, while in the control arm, these values were 92%, 84%, and 80%, respectively, and the difference was not statistically significant (P > 0.05). Disease-free survival at 3 years was 88% in the study arm and 80% in the control arm., Conclusion: The study suggests that hypofractionated regimen may be better in local control and symptomatic relief with the added advantage of shorter treatment time, which offers better patient compliance and advantageous in busy setups where there is heavy patient load., Competing Interests: None

Purpose: Photodynamic diagnosis and white-light TURB with adjuvant intravesical chemotherapy (ICT) is widely used in treatment of bladder cancer. This non-inferiority trial is designed to demonstrate non-inferiority regarding recurrence-free survival (RFS) of Hexvix ® TURB followed by immediate instillation compared to white-light TURB with immediate instillation followed by maintenance ICT., Methods: Between 07/2010 and 12/2016, 129 patients with EORTC intermediate risk non-muscle invasive bladder cancer treated with TURB were included in this multicentre phase III study. Patients were randomized and received either white-light TURB with immediate ICT followed by maintenance ICT (n = 62, 20 mg Mitomycin weekly for 6 weeks as induction phase, afterwards 20 mg/month for 6 months) or Hexvix ® TURB with immediate ICT only (n = 67, 40 mg Mitomycin). Primary study endpoint was RFS after 12 months. Hexvix ® TURB was counted as non-inferior to white light alone if the upper limit of the one-sided 95% confidence interval of hazard ratio was lower than 1.676. Due to the non-inferiority design, the per-protocol population was used as the primary analysis population (n = 113) RESULTS: Median follow-up was 1.81 years. Hexvix ® group showed more events (recurrence or death) than white-light group (19 vs. 10) resulting in a HR of 1.29 (upper limit of one-sided 95%-CI = 2.45; p non-inferiority  = 0.249). The ITT population yielded similar results (HR = 1.67); 3.18], p non-inferiority  = 0.493). There was no significant difference in overall survival between both groups (p = 0.257)., Conclusion: Non-inferiority of Hexvix ® TURB relative to white-light TURB with maintenance Mitomycin instillation in intermediate risk urothelial carcinoma of the bladder was not proven. Hence a higher effect of maintenance ICT is to assume compared to a Hexvix ® -improved TURB only, confirming its important role in patient treatment., (© 2021. The Author(s).)

Background and Aims: Biliary tract cancer (BTC) is rare and has limited treatment options. We aimed to examine aspirin use on cancer-specific survival in various BTC subtypes, including gallbladder cancer, ampulla of Vater cancer, and cholangiocarcinoma., Approach and Results: Nationwide prospective cohort of newly diagnosed BTC between 2007 and 2015 were included and followed until December 31, 2017. Three nationwide databases, namely the Cancer Registration, National Health Insurance, and Death Certification System, were used for computerized data linkage. Aspirin use was defined as one or more prescriptions, and the maximum defined daily dose was used to evaluate the dose-response relationship. Cox's proportional hazards models were applied for estimating HRs and 95% CIs. Analyses accounted for competing risk of cardiovascular deaths, and landmark analyses to avoid immortal time bias were performed. In total, 2,519 of patients with BTC were exposed to aspirin after their diagnosis (15.7%). After a mean follow-up of 1.59 years, the 5-year survival rate was 27.4%. The multivariate-adjusted HR for postdiagnosis aspirin users, as compared with nonusers, was 0.55 (95% CI: 0.51 to 0.58) for BTC-specific death. Adjusted HRs for BTC-specific death were 0.53 (95% CI: 0.48 to 0.59) and 0.42 (95% CI: 0.31 to 0.58) for ≤ 1 and > 1 maximum defined daily dose, respectively, and showed a dose-response trend (P < 0.001; nonusers as a reference). Cancer-specific mortality was lower with postdiagnosis aspirin use in patients with all major BTC subtypes., Conclusions: The nationwide study revealed that postdiagnosis aspirin use was associated with improved BTC-specific mortality of various subtypes. The findings suggest that additional randomized trials are required to investigate aspirin's efficacy in BTC., (© 2021 by the American Association for the Study of Liver Diseases.)

The tumor-stroma ratio (TSR) determined by pathologists is subject to intra- and inter-observer variability. We aimed to develop a computational quantification method of TSR using deep learning-based virtual cytokeratin staining algorithms. Patients with 373 advanced (stage III [n = 171] and IV [n = 202]) gastric cancers were analyzed for TSR. Moderate agreement was observed, with a kappa value of 0.623, between deep learning metrics (dTSR) and visual measurement by pathologists (vTSR) and the area under the curve of receiver operating characteristic of 0.907. Moreover, dTSR was significantly associated with the overall survival of the patients (P = 0.0024). In conclusion, we developed a virtual cytokeratin staining and deep learning-based TSR measurement, which may aid in the diagnosis of TSR in gastric cancer., (© 2021. The Author(s).)

Abstract: This study aimed to retrospectively analyze risk factors for the prognosis of Chinese patients with endometrial carcinoma.Total 600 patients who were admitted to the Department of Gynecology, the Fourth Hospital of Hebei Medical University and were pathologically diagnosed as endometrial carcinoma after surgery from January 1, 1997 to December 31, 2006 were selected, and the related factors affecting their prognosis were analyzed.The survival of 600 patients with endometrial carcinoma was 2 to 136.5 months (average survival 57.39 ± 33.55 months), and 109 cases (18.2%) died from endometrial cancer. The overall survival rate of 1, 3, and 5 years after surgery was 96.8%, 89.9%, and 82.1%, respectively. Univariate analysis showed that age, menopausal status, pathological type, histological grade, pathological staging, tumor size, myometrial invasion, cervical involvement, ovarian metastasis, lymph node metastasis, and treatment method were the factors affecting the prognosis of endometrial carcinoma. Multivariate regression analysis showed that pathological type, histological grade, pathological staging, and cervical involvement were independent risk factors for the prognosis of endometrial carcinoma. The patients with high-grade and deep myometrial invasion, cervical involvement, full cavity tumor, and lymph node metastasis had a high incidence of ovarian metastasis.Pathological type, histological grade, pathological staging, and cervical involvement are independent risk factors affecting the prognosis of Chinese patients with endometrial carcinoma., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The possible involvement of p53 signaling, FGFR3 expression, and FGFR3 mutation rates in the prediction of the NMIBC anti-PD-L1 treatment response needs to be clarified. The main aim of our study was to explore predictive value of p53 expression, FGFR3 expression, and its gene mutation status for the therapeutic success of anti-PD-L1 treatment in the patient-derived murine model of recurrent high-PD-L1(+) GATA3(-)/CR5/6(-) high-grade and low-grade NMIBC., Methods: twenty lines of patient-derived xenografts (PDXs) of relapsed high-PD-L1(+) double-negative NMIBC were developed, of which 10 lines represented high-grade tumors and the other ones-low-grade bladder cancer. Acceptors of each grade-related branch received specific anti-PD-L1 antibodies. Animals' survival, tumor-doubling time, and remote metastasis were followed during the post-interventional period. PD-L1, GATA3, CR5/6, and p53 protein expressions in engrafted tumors were assessed by immunohistochemistry. The FGFR3 expression and FGFR3 mutations in codons 248 and 249 were detected by real-time polymerase chain reaction., Results: The expression of p53 protein is an independent factor affecting the animals' survival time [HR = 0.036, p = 0.031] of anti-PD-L1-treated mice with low-grade high-PD-L1(+) double-negative NMIBC PDX. The FGFR3 expression and FGFR3 mutation rate have no impact on the anti-PD-L1 treatment response in the interventional groups., Conclusions: p53 expression may be considered as a prognostic factor for the anti-PD-L1 treatment efficacy of low-grade high-PD-L1-positive GATA3(-)/CR5/6(-)-relapsed noninvasive bladder cancer.

Background: Acyl-CoA dehydrogenase short-chain (ACADS) is a crucial enzyme in the fatty acid metabolism pathway located in mitochondria. However, the expression level and prognostic value of ACADS in colorectal cancer (CRC) remain unclear. Methods: The mRNA and protein expression data of ACADS was obtained from The Cancer Genome Atlas (TCGA), Clinical Proteomic Tumor Analysis Consortium (CPTAC), and Oncomine. Prognostic values of ACADS were calculated using Kaplan-Meier survival analysis. Correlations between ACADS and immune infiltration were estimated using TIMER, CIBERSORT, EPIC, quanTIseq, and xCell. The UALCAN and MEXPRESS databases were utilized for Methylation analysis. The co-expression analysis based on mRNA expression and interaction network of ACADS were performed via several online tools. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis on ACADS co-expressed genes were performed using the Metascape. Results: The expression analysis demonstrated that ACADS was down-regulated in CRC tissues compared with paired normal tissue. Expression of ACADS was found to be significantly associated with clinical cancer stages and the consensus molecular subgroups (CMS) constituent ratio in CRC patients. Besides, lower ACADS expression was found to predict poor prognosis and be significantly associated with common immune checkpoint genes and MMR genes in CRC. ACADS expression levels were positively related to B cells, CD4 + T cells, CD8 + T cells, M1 macrophages, neutrophils, and Tregs, while negatively correlated with M0 macrophages, M2 macrophages. The methylation level of ACADS in normal tissues was significantly higher than that in tumor tissues, and several methylation sites were identified. The enrichment analysis suggested the co-expressed genes mainly enriched in cell mitochondrial metabolism. Conclusions: The present study provided multilevel evidences for expression of ACADS in CRC and the function of ACADS in prognostic prediction, immune infiltration, and methylation. ACADS might have the potential as the novel biomarker and therapeutic target in CRC patients., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Tripartite motif containing 16 (TRIM16) is a member of the tripartite motif protein family and functions as a potential tumor suppressor in several cancers. However, the specific function and clinical significance of TRIM16 in colorectal cancer (CRC) remains unclear. In this study, we observed that low TRIM16 expression was detected frequently in primary colorectal cancer (CRC) tissues and was closely associated with a better prognosis. Functional studies demonstrate that TRIM16 overexpression notably inhibits the metastasis abilities of CRC in vivo and in vitro. Mechanistically, our results demonstrated that TRIM16 directly bound and ubiquitinated Snail family transcriptional repressor 1 (Snail), an important transcriptional factor of the epithelial-mesenchymal transition (EMT) process suppressing the EMT in CRC. Additionally, our data revealed that the inhibition effect of TRIM16 on cancer metastasis was dependent on Snail degradation. Collectively, our study is the first to report that TRIM16 plays a crucial anti-tumor role in CRC tumorigenesis. We also provided novel evidence that TRIM16 might act as a prognostic and therapeutic target to assess and inhibit CRC progression., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The aim of this study was to investigate the outcome of histological subtype review of high-grade endometrial carcinoma (EC) and its prognostic impact in a large well-documented Danish nationwide cohort. From the Danish Gynecological Cancer Database (DGCD) 2005-2012 cohort, we included 425 patients with an original diagnosis of high-grade EC, independent of histologic subtype. Of these, at least one hematoxylin and eosin (H&E)-stained slide from 396 cases (93.2%) was available for review. The histologic subtype was reviewed by specialized gynecopathologists blinded to the original diagnosis and clinical outcome. Interobserver variability between original and revised histologic subtypes was analyzed using simple Kappa statistics. Hazard ratios (HR), recurrence-free survival (RFS), and overall survival were calculated for original and revised subtypes, respectively. Overall histologic subtype agreement was moderate (kappa = 0.42) with the highest agreement for endometrioid-type EC (EEC; 75.5%) and serous-type EC (SEC; 63.8%). For clear cell carcinoma and un-/dedifferentiated EC, agreement was significantly lower: 30.1% and 33.3% respectively. Of the 396 reviewed cases, only two (0.5%) were re-classified as low-grade EEC upon revision. Interestingly, GR3 EEC had better RFS than SEC with stronger significance after revision (HR 2.36 (95% CI 1.43-3.89), p = 0.001), compared to original diagnosis (HR 1.74 (95% CI 1.07-2.81), p = 0.024). In conclusion, this study confirmed that pathology review results in substantial shift in histological subtype in high-grade EC. After review, a stronger prognostic benefit for GR3 EEC as compared to other histological subtypes was observed. This work supports maintaining a low threshold for pathology revision of high-grade EC in clinical practice., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To assess the efficacy and safety of dose-dense weekly paclitaxel plus carboplatin (ddTC) with or without bevacizumab compared to conventional, tri-weekly paclitaxel plus carboplatin (cTC) with or without bevacizumab, in metastatic or recurrent cervical carcinoma not amenable to curative local therapy., Methods: Patients were randomly assigned to either the cTC or ddTC arm. The cTC regimen was paclitaxel 175 mg/m 2 and carboplatin at an area under the curve (AUC) of 5 on day 1. The ddTC regimen was paclitaxel 80 mg/m 2 on day 1, 8, 15 and carboplatin at AUC of 5 on day 1. Both cTC and ddTC treatments were repeated every 3 weeks for up to 9 cycles. After bevacizumab was approved in Japan, patients in both arms received bevacizumab 15 mg/kg if not contraindicated. The primary endpoint of phase II part was response rate (RR). If the RR of ddTC+bevacizumab was found to be at least 5% better than to cTC + bevacizumab, the study would proceed to phase III part, which had overall survival as its primary endpoint., Clinical Trial Information: jRCTs031180007., Results: In total, 122 patients were randomly assigned to either the cTC arm (cTC + bevacizumab: 32; cTC:29) or the ddTC arm (ddTC+bevacizumab: 30; ddTC:31). The RR for patients on cTC + bevacizumab was 67.9%, and for patients on ddTC+bevacizumab 60.7%, cTC: 55.2%, and ddTC: 50.0%., Conclusions: The study did not meet the primary endpoint of phase II portion. Dose-dense, weekly paclitaxel plus carboplatin is not promising for metastatic or recurrent cervical carcinoma., Competing Interests: Declaration of Competing Interest None of the authors reports that they have any conflict of interest to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Concurrent chemoradiotherapy followed by brachytherapy is the standard of care in locally advanced carcinoma cervix. There is no prognostic factor at present to predict the outcome of disease in locally advanced carcinoma cervix., Aim: Differential expression of microRNAs can be used as biomarkers to predict clinical response in locally advanced carcinoma cervix patients., Methods: Thirty-two patients of locally advanced carcinoma cervix with International Federation of Gynecology and Obstetrics Stage IB-IVA were enrolled from 2017 to 2018. Expression of microRNA-9 5p, -31 3p, -100 5p, -125a 5p, -125b-5p, and -200a 5p in formalin-fixed paraffin embedded (FFPE) biopsied tissue were analyzed by real time quantitative reverse transcriptase polymerase chain reaction (RT qPCR). Pretreatment evaluation was done with clinical examination and MRI pelvis. All patients received concurrent chemoradiotherapy followed by brachytherapy. Patients were evaluated for the clinical response after 3 months of treatment, with clinical examination and MRI pelvis scan using RECIST 1.1 criteria. Patients with no residual disease were classified as Complete responders (CR) and with residual or progressive disease were classified as Nonresponders (NR). Results were statistically analyzed using Mann Whiney U test to examine significant difference between the expression of microRNA between complete responders (CR) and nonresponders (NR)., Results: microRNA-100 5p was upregulated in complete responders (CR) which showed a trend towards statistical significance (p value = 0.05)., Conclusion: microRNA-100 5p can serve as a potential molecular biomarker in predicting clinical response to chemoradiation in locally advanced Carcinoma cervix. Its role should be further investigated in a larger study population., (© 2021 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

Background: Leptomeningeal metastasis (LM) is associated with a grave prognosis in breast cancer (BC) and can be controlled with a ventriculoperitoneal shunt (VPS). Information regarding LM and VPS based on intrinsic subtype is limited; thus, we investigated the clinical outcomes of BC treated with VPS., Patients and Methods: The present retrospective study comprised 70 patients diagnosed with LM who received a VPS. The patients were divided into 4 groups based on BC subtype: hormone receptor (HR) + /human epidermal growth factor receptor 2 (HER2) - , HR + /HER2 + , HR - /HER2 + , and triple negative BC (TNBC)., Results: The most common indications for VPS were uncontrolled intracranial pressure (57.1%) and uncontrolled headache (55.7%), which improved in 54 (77.1%) of 70 patients after VPS. The median overall survival (OS) after brain or LM and overall survival after VPS were 7.6 and 2.3 months, respectively. Anti-HER2 treatment was a significant prognostic factor for better OS after brain or LM based on multivariate analysis (hazard ratio, 0.15; 95% confidence interval, 0.04-0.57; P = .005), whereas TNBC was correlated with shorter OS after central nervous system metastasis (hazard ratio, 2.82; 95% confidence interval, 1.46-5.48; P = .002)., Conclusions: There were significant differences in clinical outcome based on the intrinsic subtype of patients with BC with LM who received a VPS. Anti-HER2 treatment in patients with HER2 + BC was associated with better survival in patients with metastatic BC with VPS insertion compared with those without. Survival of metastatic BC with VPS remained poor, especially in the TNBC subgroup., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Accumulating studies have demonstrated that microRNAs (miRNAs) are involved in the progression of various cancers. This study aimed to investigate the potential clinical and functional role of miR-432 in breast cancer., Materials and Methods: We evaluated the expression of miR-432 in 117 breast cancer samples and paired nontumor tissue samples, as well as 4 breast cancer cell lines using RT-qPCR analysis. Kaplan-Meier survival curve and multivariate Cox regression analysis were used to evaluate the prognostic significance of miR-432 in breast cancer patients. CCK-8 assay and Transwell assays were used to evaluate the biological function of miR-432 in the progression of breast cancer., Results: miR-432 was downregulated in breast cancer tissues and cell lines, and its exotic expression was associated with tumor size, lymph node metastasis, and TNM stage. In addition, breast cancer patients with low miR-432 expression exhibited a shorter overall survival outcome. Further experiments revealed that overexpression of miR-432 inhibited the cell proliferation, migration, and invasion of breast cancer cells, while knockdown of miR-432 promoted these cellular activities. AXL was a direct target of miR-432 in breast cancer cells., Conclusion: The present study suggested that miR-432 may be a tumor suppressor in the progression of breast cancer through inhibiting cell proliferation, migration, and invasion by targeting AXL. And miR-432 might be a prognostic biomarker and therapeutic target for the treatment of breast cancer. This study provided a novel insight into breast cancer prognosis and treatment., Competing Interests: Disclosure The authors declare that they have no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: We assessed the long-term oncologic safety of nipple-sparing mastectomy (NSM) compared to skin-sparing mastectomy (SSM) for primary breast cancer patients with immediate reconstruction., Patients and Methods: Data of stage 0-III primary breast cancer patients undergoing NSM (n = 190) or SSM (n = 729) from June 2006 to December 2012 were retrospectively collected. Nipple-tumor distance (NTD) was measured on pretreatment mammography, magnetic resonance imaging, or ultrasonography findings. NSM patients with NTD < 1 cm were excluded. Locoregional recurrence (LRR) rates were compared between groups. Disease-free survival (DFS) and overall survival (OS) according to surgical procedure were assessed., Results: The median (range) follow-up period for NSM and SSM was 71 (10-131) months and 79 (9-140) months, respectively. LRR developed in 11 patients with invasive ductal carcinoma (5.8%) for NSM and 44 (42 in patients with invasive ductal carcinoma and 2 in patients with ductal carcinoma-in-situ) (6.0%) for SSM. Hormone receptor and HER2 status were not associated with LRR in either group. DFS and OS rates did not differ between groups (DFS: 89.3% for NSM, 89.3% for SSM, P = .87; OS: 98.4% for NSM, 94.5% for SSM, P = .43)., Conclusion: NSM with immediate reconstruction was as safe as SSM for primary breast cancer with respect to prognosis and local control, regardless of the presence of invasive carcinoma or breast cancer subtype., (Copyright © 2021 Elsevier Inc. All rights reserved.)