[Endometrial carcinoma and precursor lesions]

Endometrial carcinoma is the most common malignant tumor of the female genitals in developed countries. The differences noted in epidemiology, presentation, and biological behaviors of endometrial carcinoma suggest that there are two fundamentally different pathogenic types of the disease: type I (estrogen related, endometrioid type) and type II (non-estrogen related, non-endometrioid type). The first type is more common and represents about two-thirds of cases. It occurs in women with hyperlipidemia, obesity, and signs of hyperestrogenism, including anovulatory uterine bleeding, infertility, late onset of menopause, ovarian stromal hyperplasia, and endometrial hyperplasia. The second type occurs in the absence of these features. Pathohistologically, type I tumors are composed of endometrioid carcinoma whereas type II tumors are composed of serous or clear cell carcinoma. Atypical hyperplasia is recognized as the precursor for the endometrioid type of endometrial carcinoma and endometrial intraepithelial carcinoma (EIC) as the precursor of serous carcinoma, the most common non-endometrioid type of endometrial carcinoma. In endometrioid type of endometrial carcinoma, it appears that PTEN mutation may be central to the initiation of endometrial proliferative lesions by which damage in other genes is then accumulated (e.g., DNA mismatch repair genes, K-ras, p53) in the progression to carcinoma. In contrast to endometrioid type, p53 mutations appear to be important in the conversion of atrophic endometrium to EIC and serous adenocarcinoma. Endometrial intraepithelial neoplasia (EIN) has been a recently defined precursor for the endometrioid type of endometrial carcinoma.