Endometrial cancer

Endometrial cancer is one of the most common forms of gynecological cancer. The incidence of endometrial cancer is rising which is thought to be related to increasing life expectancy and the epidemic of obesity. Around 80 % of endometrial cancers represent endometrioid histology. These are considered hormone dependent and the prognosis of these cancers is generally favourable. The majority of endometrial cancers are detected at an early stage with disease restricted to the uterus.

Endometrial cancer originates from the endometrium (the mucosal lining of the uterus). The common form of endometrial cancer, referred to as type 1 or estrogen-related endometrial cancer, usually occurs in younger, pre-menopausal women and tends to be of lower histologic grade. Type 2, or non-estrogen-related endometrial cancer, occurs in post-menopausal women and is the more aggressive form of endometrial cancer.

High estrogen blood levels stimulate the endometrial mucosa, which may result in excessive endometrial growth and type 1 endometrial cancer. Conditions such as diabetes, infertility, obesity, and polycystic ovarian syndrome (PCOS) are associated with an increased risk to develop type 1 endometrial carcinoma. Infrequent periods, first menstruation before the age of 12, no pregnancies, and entering menopause after the age 50 may is also associated with an increased risk, as is receiving estrogen replacement therapy (without progesterone) or tamoxifen treatment (common drug for treatment of breast cancer). Factors that predispose for type 2 endometrial cancer are less well known.

Certain correlations exist between the type of endometrial cancer and histology. Type 1 cancers are usually low-grade, have an endometrioid appearance and are associated with hyperplasia in the adjacent endometrium. Type 2 usually consists of high-grade, serous or clear cell tumors and is not associated with endometrial hyperplasia.

Histologic grade in endometrial cancers is defined on the basis of tubular differentiation and nuclear pleomorphism. Well-differentiated (Grade 1) endometrial cancers show uniform oval nuclei with evenly dispersed chromatin and a solid tumor growth pattern (without lumen formation) only in a small fraction of the tumor. In poorly differentiated cancers (Grade 3) nuclei with coarse chromatin and prominent nucleoli are observed and more than 50% of the tumor is composed of solid masses.

Endometrial cancers are popularly staged according to the FIGO (International Federation of Gynaecology and Obstetrics) staging system. Stage I cancers are limited to the uterine corpus (or body). Stage II tumors involve the cervix, while Stage III tumors involve the serosa and/or uterine adnexae, vagina, and pelvic lymph nodes. In Stage IV distant metastases are present.

Immunohistochemistry for estrogen alpha (ER, ESR1) and progesterone receptors (PR, PGR) shows that these hormonal receptors are typically expressed in tumor cells in type 1, but frequently not in type 2 endometrial cancers.

Normal tissue: Endometrium