Each year, over 49,000 women are diagnosed with uterine cancer, and approximately 8000 women succumb to the disease (1). The vast majority of uterine tumors are adenocarcinomas. Less than 5% of these are uterine sarcomas.
Endometrial adenocarcinoma is more commonly diagnosed among older women with the peak incidence occurring in the sixth decade of life. It is also more commonly diagnosed in white women compared to non-white women. These cancers can be broadly categorized into two types based on clinical and pathologic factors (2):
Type I endometrial carcinomas follow an estrogen-dependent pathway. The precursor lesion is atypical hyperplasia. These tumors comprise the majority of endometrial cancers, are limited to the uterus, and have a favorable prognosis.
Type II endometrial carcinomas appear to develop independent of estrogen exposure. They occur more frequently among black women and arise in a background of atrophic endometrium. Compared to type I endometrial cancers, women tend to be diagnosed at an older age and at a later stage. They also confer a poorer overall prognosis.
Risk factors for the development of type I endometrial cancer include states related to excess estrogen stimulation. This includes nulliparity, unopposed estrogen administration, tamoxifen exposure, polycystic ovarian syndrome, and obesity. Higher parity, smoking, and use of estrogen-progestin hormonal contraception are known to decrease risk. In contrast, specific risk factors for type II endometrial cancer have not been identified.
Genetic factors contribute to only about 10% of endometrial cancers, mostly due to hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome, and, to a lesser degree, Cowden syndrome. Both of these genetic conditions follow autosomal dominant inheritance patterns. While it is not clear if individuals with BRCA 1 and 2 mutations have increased risk, there does seem to be higher risk for patients with breast cancer, perhaps because of shared risk factors.
There is no single molecular event that gives rise to endometrial cancer. However, type I and type II endometrial carcinomas are associated with distinct molecular changes: type I endometrial adenocarcinomas are associated with mutations involving the PTEN pathway or show evidence of microsatellite instability (3). Type II tumors are associated with p53 mutations and mutations involving HER2/neu (3, 4).
The World Health Organization classifies endometrial adenocarcinoma into multiple types including endometrioid, serous, and clear cell, among the more common variants (5). Another variant of endometrial carcinoma is carcinosarcoma, which is considered a high-risk histology.
Endometrioid carcinoma is the most common endometrial cancer, comprising 75%–80% of all cases. These cancers occur with varying degrees of differentiation, characterized histologically by grade. Well (grade 1) to moderately (grade 2) differentiated endometrioid carcinomas are considered type ...