The 2020 WHO Classification of Female Genital Tumours introduced the p53 mutant signature as a key molecular marker. High-grade serous carcinoma (HGSC) of the ovary shows p53 mutation in >96% of cases. The four molecular subtypes of ovarian cancer from TCGA (2011) that correlate with prognosis are: immunoreactive, mesenchymal, differentiated, and proliferative. The subtype with BEST prognosis is:

• A Immunoreactive — characterised by high expression of T-cell chemokines (CXCL10, CXCL11), immune checkpoint markers, and intratumoral TILs ✓
• B Differentiated — characterised by high HOXA9/HOXA10 expression and fimbriated end-like signatures
• C Proliferative — characterised by upregulated proliferation genes and CCNE1 amplification
• D Mesenchymal — characterised by HOX genes and N-cadherin expressing stromal cells

Explanation

The TCGA molecular classification of high-grade serous ovarian carcinoma (HGSC) identified four transcriptomic subtypes. The immunoreactive subtype has the BEST prognosis and is characterised by high expression of T-cell attracting chemokines (CXCL10, CXCL11), immune cell infiltration with high densities of tumour-infiltrating lymphocytes (TILs) including CD8+ cytotoxic T cells, and expression of T-cell activation markers and immune checkpoints (PD-L1). This immune-hot microenvironment explains better responses to platinum-based chemotherapy and potentially to immunotherapy. The mesenchymal subtype has the worst prognosis, associated with stromal signatures and immunosuppression. The proliferative subtype also has poor prognosis. The differentiated subtype is intermediate.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

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Written and medically reviewed by the StethoPrep medical team.