Histologic, Molecular, and Cytogenetic Features of Ovarian Cancers: Implications for Diagnosis and Treatment

Abstract

Ovarian epithelial carcinoma (OEC), the most common ovarian malignancy, is a heterogeneous disease with several histologic subtypes that show characteristic cytogenetic features, molecular signatures, oncologic signaling pathways, and clinical-biologic behavior. Recent advances in histopathology and cytogenetics have provided insights into pathophysiologic features and natural history of OECs. Several studies have shown that high- or low-grade serous, endometrioid, and clear cell carcinomas are characterized by mutations involving the TP53, K-ras/BRAF, CTNNB1, and PIK3CA genes, respectively. High-grade serous carcinomas, the most common subtype, often manifest with early transcoelomic spread of disease beyond the ovaries, whereas low-grade serous and mucinous carcinomas commonly manifest with early-stage disease, with a resultant excellent prognosis. On the basis of pathogenetic mechanisms, recent findings suggest a dualistic model of ovarian carcinogenesis consisting of types I and II. Type I (low-grade serous, mucinous, and endometrioid) cancers commonly arise from well-described, genetically stable precursor lesions (usually borderline tumors); manifest as large adnexal masses with early-stage disease; and have a relatively indolent clinical course, with an overall good prognosis. In contrast, type II carcinomas (high-grade serous, endometrioid, mixed, and undifferentiated variants) originate de novo from the adnexal epithelia, often demonstrate chromosomal instability, and have aggressive biologic behavior. Better knowledge of hereditary ovarian cancer syndromes and associated cytogenetic abnormalities has led to increased interest in novel biomarkers and molecular therapeutics. Genetic changes, pathologic features, imaging findings, and natural histories of a variety of histologic subtypes of OEC are discussed in this article.

Novel biomarker candidates for the diagnosis of ovarian clear cell carcinoma

“…Each histological subtype is a classified as a separate disease with characteristic cytogenetic features, molecular signatures, oncogenic signaling pathways and clinicobiological behaviors (5). Epithelial ovarian carcinomas are classified into two major subtypes, types I and II, based on their distinctive epigenetic and gene expression profiles, in addition to their functional genomic mutations.…”

“…By contrast, type II carcinomas originate de novo from the adnexal epithelia with no identifiable precursor lesion, develop rapidly and are of an aggressive nature. Type II tumors include high-grade serous, endometrioid, mixed and undifferentiated carcinomas (5). Mutations in TP53 are common in type II carcinomas and this distinction may serve as a marker of malignant growth (6).…”

The expression of miR-30a* and miR-30e* is associated with a dualistic model for grading ovarian papillary serious carcinoma

“…Low-grade serous carcinomas typically pursue an indolent course that may last more than 20 years (1,17,18). This contrasts with conventional high-grade serous carcinoma that accounts for approximately 75% of ovarian cancer but is responsible for most of the deaths (6,19) and almost always have progressed to advanced stage at diagnosis, when current available therapies are seldom curative (7,9). Women in our study had 77% high-grade, whereas only 23% had low-grade.…”

Revised FIGO staging system for cancer of the ovary, fallopian tube, and peritoneum: important implications for radiologists

“…Recently, the serous tubal intraepithelial carcinoma (STIC) theory has become widely accepted, and it may be an origin of HGSCs of the ovary and peritoneum [5][6][7][8][9]. Most ovarian cancer, especially HGSC, appear with extensive peritoneal dissemination and is often difficult to identify its origin.…”

“…LGSCs are thought to develop through a stepwise process from benign serous cystadenomas/adenofibromas to serous borderline tumors and ultimately to LGSCs, are promoted by KRAS and BRAF mutations and are unrelated to TP53 and BRCA abnormalities [5][6][7]. It has been presumed that the precursors of serous cystadenomas/adenofibromas in this low-grade ovarian pathway are ovarian surface epithelial inclusion cysts [5,6].…”