Abstract. Women with hereditary breast and ovarian cancer (HBOC) syndrome represent a unique group who are diagnosed at a younger age and result in an increased lifetime risk for developing breast, ovarian and other cancers. This review integrates recent progress and insights into the molecular basis that underlie the HBOC syndrome. A review of English language literature was performed by searching MEDLINE published between January 1994 and October 2012. Mutations and common sequence variants in the BRCA1 and BRCA2 (BRCA) genes are responsible for the majority of HBOC syndrome. Lifetime cancer risks in BRCA mutation carriers are 60-80% for breast cancer and 20-40% for ovarian cancer. Mutations in BRCA genes cannot account for all cases of HBOC, indicating that the remaining cases can be attributed to the involvement of constitutive epimutations or other cancer susceptibility genes, which include Fanconi anemia (FA) cluster (FANCD2, FANCA and FANCC), mismatch repair (MMR) cluster (MLH1, MSH2, PMS1, PMS2 and MSH6), DNA repair cluster (ATM, ATR and CHK1/2), and tumor suppressor cluster (TP53, SKT11 and PTEN). Sporadic breast cancers with TP53 mutations or epigenetic silencing (hypermethylation), ER-and PgR-negative status, an earlier age of onset and high tumor grade resemble phenotypically BRCA1 mutated cancers termed 'BRCAness', those with no BRCA mutations but with a dysfunction of the DNA repair system. In conclusion, genetic or epigenetic loss-of-function mutations of genes that are known to be involved in the repair of DNA damage may lead to increased risk of developing a broad spectrum of breast and ovarian cancers.
Introduction: The present study was a retrospective investigation of the relation between immunohistochemical BRCA1/2 status and prognosis in patients with primary peritoneal serous cancer (PPSC). Materials and Methods: We retrospectively evaluated 14 consecutive patients diagnosed with PPSC other than hereditary breast and ovarian cancer between 2005 and 2010. All patients had serum CA125 levels >40 U/mL prior to starting first-line chemotherapy with paclitaxel and carboplatin. Paclitaxel was administered as a 3-hour intravenous infusion at a dose of 175 mg/m 2 on day 1, and carboplatin was delivered at an area under the curve of 5 based on the Calvert method. Patients received six cycles of first-line chemotherapy, except patients whose disease was determined to be progressive during the chemotherapy regimen. BRCA1/2 and p53 protein expression was determined by immunohistochemistry of patient tissue samples. The Cox proportional hazards model was used to evaluate univariate and independent multivariate associations with the effect of clinical parameters, such as age at diagnosis; tumor histology; tumor grade; and rate of change in CA125, and BRCA1/2, p53 status on overall survival. Probability values of less than 0.05 were considered to indicate statistical significance. Results: Two cases (14%) had the BRCA1 mutation, and none had the BRCA2 mutation. Eleven cases (79%) were positive for p53. In the univariate analysis, factors significantly associated with overall survival were (pre-chemotherapy CA125-pre-2nd chemotherapy CA125)/pre-chemotherapy CA125 (p = 0.0034) and (pre-chemotherapy CA125-pre-3rd chemotherapy CA125)/pre-chemotherapy CA125 (p = 0.0245). BRCA1 and p53 status were not predictors of overall survival. Multivariate analysis performed with overall survival as an endpoint revealed that none of the factors examined was significant. Median survival rate of patients without a BRCA1 mutation was 23.5 months (2 -82 months), and all died. By contrast, one patient with a BRCA1 mutation remains alive at 85 months, and the other patient died at 64 months. Conclusion: BRCA1 might be a predictor of overall survival in patients with PPSC receiving chemotherapy.
A malignant solitary fibrous tumor arising from the omentum is extremely rare. To our knowledge, this is the first case of a malignant solitary fibrous omentum tumor coexisting with uterine corpus cancer. A 62-year-old woman presented to our hospital with vaginal discharge. Endometrioid adenocarcinoma was diagnosed by endometrial curettage. In addition, a solid tumor in front of the uterus was detected following computed tomography and/or magnetic resonance imaging, which was suspected to be a primary (or secondary) malignant tumor arising from the omentum. Hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and lymphadenectomy were performed. A malignant solitary fibrous tumor of the omentum and grade 3 endometrioid adenocarcinoma of the uterus were diagnosed by pathohistological analysis. Interestingly, the tumor cells were immunoreactive for p53. Adjuvant chemotherapy was administered for the uterine corpus cancer and the patient remains healthy 48 months after the surgery. These tumors may have become malignant due to the presence of p53 mutations.
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
334 Leonard St
Brooklyn, NY 11211
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.