Carcinoma of the uterine endometrium is the most common pelvic malignancy in women. The USA and Canada have the highest incidence rates in the world, whereas developing countries and Japan have incidence rates four to five times lower. Epidemiologic data indicate that there are two forms of endometrial cancer. One is directly related to estrogen exposure and is most common in the USA. The other is unrelated to estrogen and occurs throughout the world. Estrogen-related type I tumors occur among younger perimenopausal women and carry a good prognosis. In fact, type I lesions are potentially preventable through recognition of patient risk, diagnosis of the precursor lesion (atypical endometrial hyperplasia) and proper treatment. Non-estrogen-related type II tumors occur in older postmenopausal women without a history of estrogen exposure and have a poorer prognosis. The molecular genetic alterations present in type I and II endometrial carcinomas are distinct and may help to explain their clinical characteristics.
Cells of the Müllerian tract can differentiate into a wide range of tissue types. This is demonstrated by the variety of histologic subtypes seen among the endometrial cancers. The vast majority are endometrioid adenocarcinomas. Prognosis for patients with endometrioid adenocarcinoma is determined largely by its degree of differentiation or histologic grade (well, moderately or poorly differentiated). In fact, histologic grade is a prognostic factor independent of stage at diagnosis. Less common histologic subtypes include mucinous adenocarcinoma, serous adenocarcinoma, clear cell adenocarcinoma, squamous cell carcinoma and a variety of rare mixed and undifferentiated tumors. For all subtypes other than endometrioid adenocarcinoma, prognosis depends more on histologic subtype than on histologic grade.
Endometrioid adenocarcinoma first invades the stroma of the underlying uterine tissue by destroying the glandular basement membrane. It then invades the myometrium and cervix. Endometrioid adenocarcinoma typically spreads via the pelvic and periaortic lymphatic channels rather than hematogenously. Vascular invasion is usually seen only with high-grade, non-estrogen-dependent lesions.
Treatment of endometrial cancer usually involves surgical removal of the uterus, fallopian tubes and ovaries. Patients with deep myometrial invasion or disease outside of the uterus may be treated postoperatively with radiation, chemotherapy or progestin-based hormonal therapies. Pretreatment analysis of endometrioid adenocarcinoma specimens for estrogen and progesterone receptor status may help to direct postsurgical therapy. There is a good correlation between tumor differentiation and receptor content. Well-differentiated tumors usually have greater numbers of estrogen and progesterone receptors. Because receptor content predicts response to progestin therapy, patients with well-differentiated tumors may be good candidates for progestin therapy.
The survival rate for endometrial cancer is relatively good. Overall, survival approaches 70% at both 5 and 10 years. Patients with stage 1 disease, in which the tumor has not invaded through more than half the myometrial thickness, have a 5-year survival rate of over 90%. Because of its high prevalence, endometrial cancer can be considered a neoplasia of high morbidity and relatively low mortality in developed countries.
Epidemiology of endometrial cancer
Endometrial cancer is largely a disease of the postmenopausal woman. About 80% of cases diagnosed are in women aged 50–75 years of age, with peak incidence in those aged 55–70. A woman entering menopause has double the chance of developing endometrial cancer compared with her chance for developing carcinoma of the cervix or the ovary. The incidence of endometrial cancer varies dramatically from country to country. This geographic pattern follows that of breast and ovarian cancer, with the highest rates in industrialized countries. It is exactly the opposite of patterns observed for cervical cancer.
An association between estrogen exposure and endometrial cancer has been apparent for over 50 years. Many of the risk factors listed in Table 43.1 are thought to increase the risk because of their close association with high estrogen levels, typically unopposed by progesterone. The single most important and best defined risk factor for adenocarcinoma of the uterus is obesity. Adipose tissue has active aromatase enzymes. Adrenal androgens are rapidly converted to estrogens within the adipose tissue of obese individuals. These newly synthesized estrogens also have excellent bioavailability because the metabolic changes associated with obesity inhibit the production of sex hormone-binding globulins by the liver. Obese individuals may have dramatic elevations in their circulating bioavailable estrogens and this exposure can cause hyperplastic growth of the endometrium.
Table 43.1 Risk factors for endometrial cancer
| Increased risk |
| Obesity |
| Diabetes |
| High-fat diet |
| High socioeconomic status |
| Urban residence |
| Positive family history |
| Polycystic ovary syndrome |
| Unopposed estrogen replacement therapy in menopause |
| Tamoxifen use |
| Estrogen-secreting tumors |
| Decreased risk |
| Delayed menarche |
| Combination oral contraceptive use |
| Child-bearing |
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