Paper II
Question
Risk factors and classification of endometrial carcinoma
Answer
Risk factors for endometrial carcinoma
- Unopposed oestrogen exposure (the central shared mechanism for Type I tumours): obesity (peripheral aromatization of androgens to oestrogen in adipose tissue), nulliparity, early menarche/late menopause, oestrogen-only hormone replacement therapy, polycystic ovarian syndrome, oestrogen-secreting tumours (e.g., granulosa cell tumour)
- Tamoxifen use (has partial oestrogenic effect on the endometrium)
- Diabetes mellitus and hypertension (often clustering with obesity)
- Lynch syndrome (hereditary non-polyposis colorectal cancer) — significantly increased risk
- Increasing age
Classification
Type I (Endometrioid) endometrial carcinoma
- More common (~80%), associated with unopposed oestrogen excess and endometrial hyperplasia as a precursor lesion
- Typically low-grade, better prognosis
- Molecular alterations: PTEN, KRAS, PIK3CA, microsatellite instability (mismatch repair deficiency)
Type II (Non-endometrioid) endometrial carcinoma
- Less common (~20%), arises in a background of atrophic endometrium, not oestrogen-dependent, typically in older postmenopausal women
- Includes serous carcinoma and clear cell carcinoma — high-grade, more aggressive, worse prognosis
- Molecular alteration: TP53 mutation is characteristic (particularly in serous carcinoma)
Histological subtypes
- Endometrioid adenocarcinoma (most common)
- Serous carcinoma
- Clear cell carcinoma
- Mucinous carcinoma
- Carcinosarcoma (mixed epithelial and mesenchymal malignant elements)