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High-grade Serous Carcinomas, The Distal Fallopian Tube as the Origin of Non-uterine Pelvic (Scientific Impact Paper No. 44)

Published: 19/11/2014

Epithelial ovarian cancers (EOCs) are the most common cause of death from gynaecological malignancy in the developed world. EOCs comprise a heterogeneous group of neoplasms including serous (68%), clear cell (13%), endometrioid (9%) and mucinous (3%) pathological subtypes.

Serous ovarian carcinomas are further divided into low-grade (type I) and high-grade (type II) serous ovarian carcinomas (LGSOC and HGSOC, respectively). Most deaths are attributable to HGSOC which is approximately 20 times more common than LGSOC.

The lifetime risk of developing EOC is 1 in 70 (1.4%) by 75 years of age, with the main risk factors being advancing age and family history. Approximately 10–25% of ovarian cancers are associated with an identified hereditary genetic abnormality. Mutations in the BRCA1 or BRCA2 genes are the most common hereditary genetic abnormalities and are associated with a 50% and 25% lifetime risk by the age of 75 years respectively.

The carcinomas that develop in patients with hereditary BRCA1 or BRCA2 mutation are commonly high-grade serous in type. After the introduction of platinum-based chemotherapy in the late 1980s, there has been little further improvement in survival from EOC. The overall survival at 5 years is 43%. However, if confined to the fallopian tube or ovary, survival can be as high as 80–95% at 5 years.

Surgery and chemotherapy remain the main treatment modalities. Screening strategies have had little impact to date because the pathogenesis of EOC has been poorly understood and no precursor lesion has been identified.