Endometrial Carcinoma

The successful focus of cytology on the reduction of cervical ­carcinoma among women through intensive prospective screening has changed the proportion of uterine cancer distribution within the United States. Endometrial cancers are now the most frequently diagnosed malignancies of the female genital tract, with 40,100 new cases of uterine corpus cancer projected for 2008. Our descriptions of endometrial neoplasia rest on our observations of 168 contemporaneously gathered hysterectomy-controlled cases and 72 office-based samplings, 127 of which represented outspoken endometrial cancer (see Table 8.1).

In 1983, a dualistic model of endometrial tumorigenesis was proposed based on clinical observations and clinicopathologic correlations. The majority of endometrial cancers (>70%), the endometrioid adenocarcinomas, were designated as type 1 carcinomas, and these follow an estrogen-related pathway. They often arise in the background of hyperplastic endometrium, show endometrioid differentiation, and are usually low grade, having a favorable clinical outcome. The tumors usually have an indolent course and frequently are preceded by endometrial intraepithelial neoplasm (EIN). In comparison with the serous and clear cell carcinomas, the type 2 tumors develop on average 10 years later. In comparison, the endometrioid tumors are better differentiated, more likely to have diploid DNA content, less myometrial invasion, and low potential for lymphatic spread; frequently maintain estrogen and progesterone receptors; and carry a generally favorable prognosis. Four major genetic events are responsible for endometrioid tumorigenesis and include silencing of the PTEN tumor suppressor gene, microsatellite instability caused by altered mismatch repair genes, mutation of the K-ras proto-oncogene, and alterations of the beta-catenin gene.