Clinics in obstetrics and gynaecology最新文献

Like breast carcinomas, endometrial carcinomas are derived from sex steroid target tissue. Progress and research directed into the clinicopathologic relationship of steroid receptors and endometrial carcinomas have been hampered by many factors, including: limited numbers of patients with advanced-stage disease compared to the number with breast carcinoma; contamination of specimens with surrounding benign endometrial components which may contribute to total steroid binding; and amount of tissue required for standard biochemical assays. Nevertheless, several clinicopathological associations have been made for steroid receptor content of endometrial carcinomas. Receptor content appears to correlate with histological differentiation in that well-differentiated lesions have higher mean levels of receptor and more receptor 'positive' lesions than do poorly differentiated lesions. Furthermore, receptor levels and status appear to correlate with prognosis of primary endometrial carcinomas and response to hormonal therapy of advanced endometrial carcinoma. Newer techniques utilizing monoclonal antibodies to directly localize receptor in tissue specimens may lead to a greater understanding of the dynamics of receptor physiology in endometrial carcinomas, and may make possible more accurate predictions of clinical behavior by allowing the direct analysis of the receptor content of the malignant component within a tissue specimen.

Endometrial carcinoma includes several specific subtypes which have differing prognostic implications. The two most common subtypes are adenocarcinoma, not otherwise specified (NOS), and adenoacanthoma. Also included in the adenocarcinoma NOS are secretory carcinoma and mucinous carcinoma which have the same natural history as do adenocarcinomas without these features. Fortunately, the above types have the best prognosis and constitute approximately 80% of all endometrial carcinomas. They also present the major diagnostic problem for the pathologist in distinguishing atypical hyperplasia and some of the metaplasias from well-differentiated carcinoma. The tendency would appear to be the over-interpretation of these hyperplastic lesions. Other subtypes have a much less favorable outlook. They include papillary carcinoma, adenosquamous carcinoma, glassy cell carcinoma and clear cell carcinoma. There are two distinct types of papillary carcinoma, the papillary clear cell and the papillary nonclear cell carcinoma. These can readily be separated, and should be, on the basis of prognostic implications. Other pathologic parameters play a significant role in patient management and in the estimation of prognosis. These include postsurgical pathological staging, measurement of depth of myometrial invasion, lymphatic and blood-vascular invasion, serosal involvement, local spread and, perhaps most importantly, tumor grade. Nuclear grading proved to be a better predictor of treatment outcome than did either the FIGO or WHO grading systems. This was especially true in adenocarcinoma NOS, adenoacanthoma and papillary carcinoma.

Endometrial carcinoma is now the most common gynecologic cancer in the United States and its incidence is increasing. Many investigators attribute this to exogenous factors over which little control has been exerted in the western world. Obesity, dietary fat content, and changing patterns of parity and lifestyle seem significant. Moreover, there appears to be an emerging virulence noted, particularly in some centers. Improved surgical staging and a better understanding of virulence factors will increase the number of patients requiring treatment to fields larger than heretofore recognized. We can expect that one third of the patients with endometrial cancer will require treatment for widespread disease or recurrent disease. Progestational treatment is useful in approximately one-third of all patients with recurrent disease. Thus, systemic nonhormonal chemotherapy must be developed if cure rates in this disease are to improve appreciably. In 1974, only 126 patients had been reported to have been treated with cytotoxic chemotherapy for endometrial cancer. Since that time, experience has demonstrated that the most active single agents are adriamycin, cisplatin, and hexamethylmelamine. These drugs produce a 30-40% response rate when used individually. Multidrug regimens employing various combinations have achieved responses of 15-85% with and without the inclusion of a progestational agent. The median duration of response has been increased but cures are still relatively few. Adverse effects are tolerable and age is not a contraindication to the administration of cytotoxic chemotherapy. Adjuvant treatment is being tested and optimism for future success is justified.