Image by National Cancer Institute

Types of Ovarian Cancer

What are the 4 sub-types of Ovarian Cancer?

Invasive epithelial ovarian cancer represents 90% of all malignant ovarian tumors and comprises four major histological subtypes: High-grade serous, endometrioid, clear cell and mucinous ovarian cancer. Each histotype show differences in their clinical courses and survival rates. There are also two main histological subtypes of benign disease: Low grade serous  and low malignant potential ovarian cancer. Different histotypes have distinct cells of origin and can be characterized by different germline and somatic genetic changes that result in the perturbation of different molecular pathways. Even within each of the different histotypes there may be significant clinical and molecular heterogeneity.
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High Grade Serous Ovarian Cancer

High grade serous is the most common and the most lethal histotype of ovarian cancer. Tumors almost invariably acquire P53 mutation, DNA double strand break (DSB) repair deficiency and a genomic instability phenotype. High grade serous ovarian cancers are the predominant histotype that develops in patients carrying germline pathogenic mutations in DSB repair genes including BRCA1, BRCA2, BRIP1, RAD51C and RAD51D. Evidence indicates that high grade serous tumors originate from fallopian tube secretory epithelial cells which transform into the precursor lesion serous tubal intra-epithelial carcinomas (STICs) en route to high grade serous ovarian cancers 

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Mucinous Ovarian Cancer

Mucinous ovarian cancer is a rare tumor type accounting for approximately 3% of all epithelial ovarian cancers. These tumor are characteristically diagnosed at a younger age than patients diagnosed with other histotype of invasive disease. The tissues and cells of origin of mucinous ovarian cancers remain unknown, but their characteristic morphology and mutational targets in disease progression (i.e. the oncogenes RAS and BRAF) suggest they may derive from tissues with gastrointestinal lineages

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Clear Cell Ovarian Cancer

Clear cell ovarian carcinomas represent 5-10% of invasive ovarian cancer with higher rates in Asian population (~11 percent) compared Europeans (~5 percent) and African Americans (~3 percent). Women dignosed with endometriosis are at a particularly increased risk of developing clear cell ovarian cancers  suggesting that endometriotic lesions are a benign precursor for this histotype. Clear cell ovarian cancers have a distinct biology compared to high grade serous  and mucinous tumors which may also reflects the different spectrum of gene mutations associated with cancer developed, which includes ARID1A, PIK3CA, TERT and the mismatch repair genes

Endometrioid Ovarian Cancer
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Endometrioid ovarian cancers represent 2 to 4 percent of all invasive epithelial ovarian tumors. Etiologically they share many similarities with clear cell ovarian cancers: They occur more frequently in Asian populations compared to Europeans and African Americans and in women with a history of endometriosis; and they share a similar spectrum of gene mutation targets associated with cancer progression (e.g. ARID1A, PIK3CA, mismatch repair genes). High grade endometrioid and high grade serous ovarian cancers can appear pathologically similar which may reflect differences in the reporting of gene mutation frequencies and the prevalence of  endometrioid ovarian cancers more generally.