[Metastatic mechanisms of uterine malignancies and therapeutic consequences]

Abstract

Malignancies of the uterus metastasize by direct invasion of neighboring structures, lymphatically or hematogenously. Endometrial and cervical cancers lymphatically spread to the pelvic and para-aortic lymph nodes. For endometrial cancer the depth of myometrial invasion, lymphosvascular space involvement (LVSI) and a microcystic, elongated and fragmented (MELF) glandular invasion pattern are predictors for lymph node metastases. Metastases to the pelvic lymph nodes occur in approximately 10 % of endometrial cancer patients and in 30 % of these cases the para-aortic lymph nodes are also involved. Sentinel lymph node biopsy is possible for clinical stage I endometrial cancer and early stages of cervical cancer but is not yet routine. The presence of LVSI is considered to be the strongest predictor of distant metastases, particularly if assessed by immunohistochemistry with antibodies against factor VIII-related antigen or CD31. Endometrioid and clear cell carcinomas can hematogenously metastasize to the lungs, bones, liver and brain and can rarely be manifested as a solitary metastasis. In contrast, serous carcinomas can show extensive peritoneal spread. To date molecular biomarkers cannot predict the occurrence of distant metastasis. Overexpression of P53, p16 and L1CAM have been identified as negative prognostic factors and are associated with the prognostically unfavorable serous tumor type. The metastatic spread of squamous cell cervical cancer is strongly associated with tumor volume. Microinvasive carcinomas have a very low rate of parametrial and lymph node involvement and do not require radical hysterectomy. In contrast, lymph node metastases occur in up to 50 % of bulky stages IB and II cervical cancers. Distant metastases can occur in the lungs, liver, bones and brain. Molecular biomarkers have not been shown to predict metastatic spread. In well-differentiated adenocarcinoma of the cervix the pattern of invasion is strongly predictive for the presence of lymph node metastases, irrespective of tumor size and depth of invasion.

Keywords: Cervical cancer; Endometrial cancer; Metastasis; Prognostic factors; Uterine malignancies.