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• W2550828171 abstract "Ovarian carcinoma represents a heterogeneous group of malignant epithelial tumors which could be divided into two fundamental groups: Type I (endometrioid carcinoma, clear cell carcinoma, low grade serous carcinoma, mucinous carcinoma and more rare seromucinous carcinoma and malignant Brenner tumor) and type II (high grade serous carcinoma - HGSC). HGSC is the most frequent ovarian carcinoma which may be etiologically linked to inactivation of tumor suppressor genes BRCA1/2 and TP53 and differs from type I carcinomas by higher aggressiveness, tendency to peritoneal spread and worse prognosis. A precursor lesion of HGSC was described as a serous tubal intraepithelial carcinoma (STIC) which is usually localized in fimbria of the fallopian tube from where tumor cells are capable to implant on ovary and pelvic peritoneum. Therefore, HGSC may present itself not only as a tuboovarian tumor but also as a primary peritoneal carcinoma. HGSC constitutes a dominant group within hereditary ovarian carcinomas as a manifestation of hereditary breast and ovarian cancer or site-specific ovarian cancer syndromes which are associated with germinal mutations of BRCA1/2 genes. BRCA1 deficient HGSC show characteristic histological appearance which encompasses SET features (Solid-pseudoEndometrioid-Transitional), significant nuclear atypia and mitotic activity, geographic necrosis, marked lymphocytic infiltration and abnormalities in TP53 expression. Use of immunohistochemistry as a screening method for BRCA1/2 inactivation is questionable at this time. Bilateral adnexectomy is considered to be a standard prophylactic treatment of women affected by germinal BRCA1/2 mutation. In that case, fallopian tubes should be submitted completely for the histological evaluation according to the SEE-FIM protocol (Sectioning and Extensively Examining the FIMbria) due to the risk of STIC or occult HGSC. Tumors with BRCA1/2 inactivation show a better therapeutic response to platinum-based chemotherapeutic compounds and a more favorable prognosis. Inhibitors of poly(ADP-ribose) polymerase (PARP) are the next generation of antitumor agents comprising olaparib which is implemented in clinical practice currently. Germinal or somatic inactivation of BRCA1/2 serves as a predictor for targeted oncologic therapy by PARP inhibitors, therefore evaluation of these genes in ovarian carcinoma patients will be carried out by departments of pathology and clinical genetics. Next generation sequencing seems to be an ideal method for the reduction of the time factor and optimization of BRCA1/2 analysis. Unfortunately, a routine test for the evaluation of homologous recombination functionality and detection of BRCAness in sporadic tumors is still not available." @default.
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• W2550828171 date "2016-11-22" @default.
• W2550828171 modified "2023-09-23" @default.
• W2550828171 title "[Oncopathological aspects of BRCA1 and BRCA2 genes inactivation in tumors of ovary, fallopian tube and pelvic peritoneum]." @default.
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