Ovarian low-grade serous carcinomas are thought to evolve in a stepwise fashion from ovarian epithelial inclusions, cystadenomas, and borderline tumors. The current study was designed to gain insight into the origins of low-grade serous carcinomas (tubal versus ovarian) by comparatively evaluating the morphologic (secretory and ciliated cell distribution) and immunophenotypic (using antibodies to PAX8, tubulin, calretinin, and Ki67) attributes of its putative precursor lesions, the normal tubal epithelium, and the overt malignancy. A total of 226 adnexal tissues from 178 patients were studied, including 98 adnexae removed for non-neoplastic indications, 48 serous cystadenomas, 42 serous borderline tumors, and 38 low-grade serous carcinomas. Normal distal tubal epithelium comprised an admixture of PAX8 þ /tubulinÀ secretory cells and PAX8À/ tubulin þ ciliated cells with a proliferative index of B3%. The vast majority of ovarian surface epithelia displayed a mesothelial phenotype (calretinin þ /PAX8À/tubulinÀ) and low proliferative index (0% (12 per 1000)), although 4% of cases also displayed foci with tubal phenotype (calretininÀ/PAX8 þ /tubulin þ ). In contrast, most (78%) of the ovarian epithelial inclusions displayed a tubal phenotype and had a significantly higher proliferative index (1%) than ovarian surface epithelium, indicating that in most cases, the ovarian surface epithelium and ovarian epithelial inclusions are of different lineages. There was a progressive decrease in the population of ciliated cells, as evidenced by increasing secretory/ciliated cell ratio, from ovarian epithelial inclusions/cystadenomas to borderline tumors to low-grade serous carcinoma, indicating that the latter is a clonal expansion of secretory cells. Overall, the findings make a strong argument that the ovarian epithelial inclusions with a tubal phenotype is likely derived from fallopian tube through an intraovarian endosalpingiosis rather than through Mullerian metaplasia from ovarian surface epithelium. Genetic and molecular studies are needed to further confirm this finding as tubal origination of ovarian serous cancers will have a significant impact on ovarian cancer prevention and management.
BackgroundMost intrahepatic cholangiocarcinoma (ICC) patients experienced tumor recurrences even after curative resection, but the optimal cut-off time point and the specific risk factors for early and late recurrences of ICC have not been clearly defined. The objective of the current study was to define specific risk factors for early and late recurrences of ICC after radical hepatectomy.MethodsIncluded in this study were 259 ICC patients who underwent curative surgery at our hospital between January 2005 and December 2009. Recurrences in these patients were followed-up prospectively. Piecewise regression model and the minimum P value approach were used to estimate the optimal cut-off time point for early and late recurrences. Then, Cox’s proportional hazards regression model was used to identify specific independent risk factors for early and late recurrences.ResultsEarly and late recurrences occurred in 130 and 74 patients, respectively, and the 12th month was confirmed as the optimal cut-off time point for early and late recurrences. Cox’s proportional hazards regression model showed that microvascular invasion (HR = 2.084, 95% CI 1.115–3.897, P = 0.021), multiple tumors (HR = 2.071, 95% CI 1.185–3.616, P = 0.010), abnormal elevation of serum CA19-9 (HR = 1.619, 95% CI 1.076–2.437, P = 0.021), and the negative hepatitis B status (HR = 1.650, 95% CI 1.123–2.427, P = 0.011) were independent risk factors for early recurrence, and HBV-DNA level > 106 IU/mL (HR = 1.785, 95% CI 1.015–3.141, P = 0.044) and a hepatolithiasis history (HR = 2.538, 95% CI 1.165–5.533, P = 0.010) contributed to late recurrence independently.ConclusionSpecific risk factors and mechanisms may relate to early and late recurrences of ICC after curative resection.
NRF2 is the master transcriptional activator of cytoprotective genes and Kelch-like ECH-associated protein 1 (Keap1), a biosensor for electrophiles and oxidation, promotes NRF2 degradation in unstressed conditions. SQSTM1/p62, an oncogenic protein aberrantly accumulated in hepatocellular carcinoma (HCC), binds and sequestrates Keap1, leading to the prevention of NRF2 degradation. Here, we show that p15INK4b-related sequence/regulation of nuclear pre-mRNA domain-containing protein 1A (RPRD1A) is highly expressed in HCC tumors and correlated with aggressive clinicopathological features. RPRD1A competitively interacts with TRIM21, an E3 ubiquitin ligase of p62, resulting in the decrease of p62 ubiquitination and the increased sequestration for Keap1. Therefore, RPRD1A enhances the nuclear translocation of NRF2, which induces gene expression for counteracting oxidative stress, maintaining cancer cells survival, and promoting HCC development. Moreover, disturbing the redox homeostasis of cancer cells by genetic knockdown of RPRD1A sensitizes cancer cells to platinum-induced cell death. Our study reveals RPRD1A is involved in the oxidative stress defense program and highlights the therapeutic benefits of targeting pathways that support antioxidation.
OBJECTIVE To investigate the clinicopathologic features of atypical endometriosis (AEM), and to discuss the relations between AEMs and tumors. METHODS A retrospective analysis was performed on 163 cases of AEMs. The changes in the glandular epithelium, stroma, and their background and the relationship with coexisting tumors were observed. RESULTS The AEMs account of for 4.4% (163/3,724) of the endometriosis (EM) cases. Of 172 AEM foci of 163 patients, 168 were in the ovary, and the other 4 were in the fallopian tube, cervix and uterine serosa. Of the cases of ovarian EM, 6.8% were AEM. All of the 27 cases (15.7%) of the AEMs associated with a tumor were found in the ovaries, of which 15 were malignant, 9 borderline, and 3 benign. Of the ovary AEMs, 14.9% were associated with a borderline or malignant tumor. The AEM epithelia were mainly arranged in the form of surface epithelia, with only a few glands. Present were characteristic features of moderate to marked pleomorphism, epithelial tufting, bud or firework-like structures on microscopy. Epithelial metaplastic changes were observed in 86 cases (50%) of the 172 AEM foci. Epithelium, endometrioid stroma, and fibrotic-collagen formed a three-layer structure in the wall of the AEM cysts. The endometrioid stroma were usually thin compared to the fibro-collagen tissue. The transformation from an AEM to a tumor was found in most of the malignant tumors. CONCLUSIONAEM lesions have some features which are similar and also differ from both of the tumor and EM. AEMs have a relative higher potential for tumorigenesis and canceration, especially for ovarian cancer. The process of damage, repair, and scarring in EM foci over a long period may play a role in the development of EM into AEM and eventally into tumor formation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.