Prognostic Factors in Carcinosarcoma of the Female Genital Tract: A Clinicopathologic and Immunohistochemical Analysis of 27 Cases

Abstract

Carcinosarcoma of the female genital tract is a rare and highly malignant neoplasm comprising histologically epithelial and mesenchymal components. Clinicopathologic factors potentially associated with this tumor were evaluated retrospectively using a data set of 27 patients at the Istanbul University Medical School Hospital during 1995 to 2004. Carcinosarcoma occurred in the uterus in 13 cases, in the ovary in 12 cases, in the ovary and uterus in 1 case, and in the fallopian tube in 1 case. For each tissue section, immunohistochemical expression levels of estrogen receptor (ER), progesterone receptor (PR), Ki-67, p53, and p63 were determined separately for the epithelial and mesenchymal components by the percentage of cells staining positively. Multivariate analysis with the Cox proportional hazards model was used to establish statistical significance for the censored data. The results show that age older than 62 years (median) (P = .006), FIGO stage more than II (P = .003), and epithelial Ki-67 expression percentage (P = .016) were independently associated with shortened survival and that epithelial ER expression percentage (P = .04) along with epithelial p63 expression percentage (P = .008) were independently associated with longer survival. Because epithelial ER and PR expression percentages had a significantly positive correlation, they were entered separately in the model to prevent multicollinearity resulting in borderline significance (P = .053) for the PR expression level's association with longer survival. Interaction terms of the aforementioned factors with the location of the tumor revealed no statistical significance, implying that the noted associations apply generally to all carcinosarcomas of the female genital tract. Other variates considered but that have no significant association with survival include expression levels of the aforementioned markers in the mesenchymal component, p53 expression level, tumor size, depth of myometrial invasion, presence of the heterologous component, and histologic types of the carcinomatous component. The prognostic factors identified in this study may improve clinical decision making concerning adjuvant treatment of female patients with genital carcinosarcoma. Furthermore, the identification of the level of ER and, to a less extent, PR expression as positive prognostic factors for survival may present a potential therapeutic target for this highly aggressive tumor type.