Gene

Microsatellite

Carcinoma

Biology

Apoptosis

Mutation

Clear cell

Cancer research

Microsatellite instability

Genetics

ARID1A

PTEN

Serous fluid

Endometriosis

KRAS

Medicine

Allele

PI3K/AKT/mTOR pathway

Clear cell carcinoma

Pathology

Human Pathology

Based on histopathology and molecular genetics, ovarian carcinomas are divided into five main types: high-grade serous (70%), endometrioid (10%), clear cell (10%), mucinous (3%), and low-grade serous (<5%) carcinomas. These tumors, which account for over 95% of cases, represent distinct diseases with different prognoses and treatments. TP53 mutations are identified in almost all (96%) high-grade serous carcinomas (HGSCs). Early p53 loss followed by BRCA loss leads to deficiency in homologous recombination (DHR) repair, which in turn triggers chromosomal instability and widespread somatic copy number changes. An undetermined number of cases of HGSCs originate in the tubal fimbria; however, an origin from the ovarian surface epithelium cannot be totally excluded. Low-grade serous carcinomas (LGSCs) most likely represent progression of SBTs. BRAF or KRAS mutations occur in one-third to one-half of cases. Mucinous carcinomas (MCs) typically show benign-appearing, borderline, non-invasive and invasive components indicating tumor progression. KRAS mutations occur in 43.6% of cases and overexpression/amplification of HER2 in 18.8%. Endometrioid and clear cell carcinomas (EC and CCC) originate from ovarian endometriosis. Compared with their uterine counterparts, ECs have a similar frequency of β-catenin abnormalities but lower rate of microsatellite instability (MI) and PTEN alterations. ARID1A mutations occur in both ECs (30%) and CCCs (50%) and may be encountered in adjacent endometriosis. CCCs carry inactivating PTEN mutations and activating mutations in PIK3CA in 8% and 33% of cases, respectively. This review summarizes recent advances in the molecular pathology, which have greatly improved our understanding of the biology of ovarian carcinomas and are also relevant to patient management.

Ovarian carcinomas: at least five different diseases with distinct histological features and molecular genetics