High-grade serous carcinoma (HGSC) is a type of tumour that arises from the serous epithelial layer in the abdominopelvic cavity and is mainly found in the ovary. HGSCs make up the majority of ovarian cancer cases and have the lowest survival rates. HGSC is distinct from low-grade serous carcinoma (LGSC) which arises from ovarian tissue, is less aggressive and is present in stage I ovarian cancer where tumours are localised to the ovary. Although originally thought to arise from the squamous epithelial cell layer covering the ovary, HGSC is now thought to originate in the Fallopian tube epithelium. HGSC is much more invasive than LGSC with a higher fatality rate - although it is more sensitive to platinum-based chemotherapy, possibly due to its rapid growth rate. In rare cases, HGSCs can develop from LGSCs, but generally the two types arise independently of each other. More than 20% of ovarian cancer tumours have hereditary origin. The majority of these feature mutations in the tumour suppressor BRCA genes, which tend to give rise to HGSC. A mutation in BRCA1 or BRCA2 can confer a lifetime ovarian cancer risk of 40-50% and 10-20% respectively, with BRCA2 mutations strongly associated with better clinical outcomes. A specific tumour protein 53 (TP53) expression pattern in the Fallopian tube epithelium – the ‘p53 signature’ - is thought to be a precursor marker of HGSC. TP53-/- mice (in which the TP53 gene has been deleted) do not develop ovarian carcinomas. However, TP53 mutations were found in 96% of HGSC cases. A local abnormal TP53 expression may thus be indicative of HGSC. In women, pelvic HGSC show either a complete absence of P53 expression, or overexpression, suggesting that any aberration of P53 leads to tumour development. Additionally, overexpression of TP53 is associated with better clinical outcome whereas an absence of the p53 protein is linked to an increased risk of HGSC tumour recurrence. A recent mouse model suggest that a p53 mutation may induce HGSC arising from the ovary rather than the Fallopian tube. HGSC are further distinguished from LGSC by ‘type I/II’ ovarian tumour nomenclature; type I referring to tumour types (e.g. LGSCs) where precursor lesions within the ovary have been characterised, and type II referring to tumour types (e.g. HGSCs) without association of such lesions, tumours understood to develop de novo from the tubal and/or ovarian surface epithelium. This classification has more relevance to research rather than to clinical practice.

The serous membrane is a particular type of secretory epithelium which covers organs in body cavities and secretes serous fluid to reduce friction from muscle movement. Serous membrane lining the abdominopelvic cavity is called the peritoneum; that lining heart and mediastinum is the pericardium, and that lining the thoracic cavity and lungs is the pleura. Technically a ‘serous carcinoma’ can occur anywhere on these membranes, but high-grade serous carcinoma is generally limited to the peritoneal area.

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