page_title: High-grade serous carcinoma
section_title: Cell origin
hierarchical_section_title: High-grade serous carcinoma / Pathophysiology / Cell origin
caption_attribution_description: English: Top half depicts how a stem cell in the ovarian surface epithelium may become enclosed in the ovary during ovulation and form part of a cortical inclusion cyst (CIC). This cyst may then undergo Mullerian metaplasia followed by malignant transformation into a Type I tumour (i.e. one that has a precursor). Alternatively the CIC may simply undergo malignant transformation and develop into a Type II tumour (such as HGSC) de novo. Lower half of image describes how a fimbrial stem cell (or insome cases a serous tubal intraepithelial carcinoma) may become enclosed in the ovary during ovulation and form part of a cortical inclusion cyst that can undergo malignant transformation into a Type II tumour.
context_page_description: High-grade serous carcinoma 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 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.
context_section_description: 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.
  While until recently HGSC was thought to arise from simple differentiation of cortical inclusion cysts (CICs) of ovarian surface epithelium (OSE), the cell origin of HGSC is now understood to be much more complex, with evidence for other sites of origin, both intra- and extra-ovarian, having come to light.
  The common Müllerian origin of the Fallopian tubes, uterus, cervix, and upper vagina has resulted in the proposal that peritoneal high-grade serous carcinoma is a spectrum of a single disease.
  Relevant animal models of HGSC can only be developed when the cell origin is properly understood. However, as HGSC tends to have the same clinical behaviour, regardless of its primary cell origin, determining cell origin is less important for clinical treatment, but may be of relevance when looking for biomarkers.
  The specific process by which a HGSC arises may be related to the BRCA mutation status of the individual, as well as the p53 mutation status.
  A 2007 paper describes the process of determining cell of origin as “Tumour origin is typically assigned to the organ presenting with the dominant tumour mass. The one exception is the peritoneum, which is classified as a primary site only if a candidate origin is not found in the endometrium, tube or ovary”.
  It is recognised that HGSC can have variable and complex primary origins, but understanding and determining this will give insight into its pathogenesis.
caption: Diagram of HGSC theories of origin
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