Ovarian and Uterine Carcinosarcomas A Comparative Analysis of Prognostic Variables and Survival Outcomes
ABSTRACT Carcinosarcomas (malignant mixed Mullerian tumor) of the female genital tract are rare tumors associated with poor outcome. The objective of this study was to identify site-specific differences by comparing carcinosarcomas originating in the uterus and the ovaries.
Data on patients with uterine and ovarian carcinosarcomas were extracted from the Surveillance, Epidemiology, and End Results database between 1988 and 2005. Kaplan-Meier log rank and Cox proportional hazards models were used for survival analysis and for identification of possible predictors for survival.
The identified cohort included 3683 women of whom 2759 (75%) have uterine carcinosarcoma and 924 (25%) have ovarian carcinosarcomas. The patients with uterine carcinosarcoma were older than the patients with ovarian carcinosarcoma (median age, 67 vs 65 years; P < 0.001). The women with uterine carcinosarcoma compared with those with ovarian carcinosarcoma were more often African American (17.3% vs 6%; P < 0.001) and presented more often with localized disease (47% vs 10.8%; P < 0.001). Uterine carcinosarcoma compared with ovarian carcinosarcoma differed significantly with regard to the performance of lymphadenectomy (62.6% vs 41.2%; P < 0.001) and the administration of radiotherapy (38.2% vs 4.8%; P < 0.001). When controlled for the extent of disease spread, uterine carcinosarcoma had a more aggressive clinical course and shorter survival compared with ovarian carcinosarcoma. Although age (P < 0.001), race (P = 0.01), stage (P < 0.001), lymphadenectomy (P < 0.001), and radiation (P < 0.001) were all significant prognostic factors in uterine carcinosarcoma, only age (P < 0.001), stage (P < 0.001), and lymphadenectomy (P < 0.001) were significant predictors in ovarian carcinosarcoma.
Although uterine carcinosarcoma presents at an earlier stage than ovarian carcinosarcoma, it has a worse prognosis compared with ovarian carcinosarcoma, with a similar extent of disease spread. Improved survival observed in lymphadenectomy group lends support to its routine performance in patients with uterine and ovarian carcinosarcomas.
- SourceAvailable from: Darrell R Borger
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- "While these tumors exhibit similar histologic hallmarks across anatomic sites, it is unclear whether they are molecularly similar diseases. Recently, uterine carcinosarcoma was associated with worse survival and a more aggressive clinical course when compared to ovarian carcinosarcoma after adjustment for stage of disease . This raises the question of whether distinct molecular drivers of neoplasia are associated with a specific gynecologic site of origin, which can account for differential clinical behavior. "
ABSTRACT: Gynecologic carcinosarcoma is an aggressive malignancy that requires more effective treatment approaches. However, therapeutic implications regarding the specific gynecologic site of origin and the admixture of carcinomatous and sarcomatous elements that define this tumor remain uncertain. Therefore, broad genotyping was performed to identify tissue-specific somatic mutational profiles that may help direct targeted therapies in this complex neoplasia. Genotyping was conducted on primary gynecologic carcinosarcomas arising from various disease sites (uterus, ovary, fallopian tube, vagina) and within isolated histological subcomponents. Nucleic acids extracted from diagnostic tissue were used in a genotyping platform that simultaneously queried >120 common mutations across 14 cancer genes. Mutational status was correlated with clinical variables using logistic regression and Kaplan-Meier survival estimates. Cancer gene mutations were identified in 46% of the 52 patient cohort and include TP53 (23%), PIK3CA (19%), KRAS (15%), CTNNB1 (4%) and NRAS (2%). Mutation in a single gene was observed in 31% of patient samples, while synchronous mutations involving 2 and 3 genes were noted in 13% and 2% of samples, respectively. Comparative evaluation of the carcinomatous and sarcomatous elements within a tumor demonstrated a similar mutation signature. Mutations in PIK3CA, KRAS and NRAS were exclusive to tumors of uterine origin and age-adjusted Cox proportional hazards modeling associated advanced age, stage and TP53 mutations with decreased survival in the uterine subset. While carcinosarcomas across gynecologic disease sites are histologically similar, therapeutically relevant mutations in the mitogen-activated protein kinase and phosphatidylinositol 3-kinase pathways predominated in carcinosarcomas arising in the uterus.Gynecologic Oncology 12/2010; 121(1):212-7. DOI:10.1016/j.ygyno.2010.11.039 · 3.69 Impact Factor
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ABSTRACT: Uterine carcinosarcomas (UCSs), formerly known as malignant mixed müllerian tumors, are uncommon neoplasias that account for <5% of uterine malignancies. Traditionally, UCSs have been considered a subtype of sarcoma and the staging system and adjuvant oncological treatments used have been similar to those used for high-grade uterine sarcomas. However, there is now enough clinical, pathologic, and biological evidence to consider UCSs more closely related to high-grade endometrial carcinomas. Thus, these tumors should be staged based on the surgicopathologic staging system used for endometrial carcinomas. Morphologically, UCSs are heterogeneous biphasic tumors composed of an admixture of malignant (endometrioid and nonendometrioid) epithelial and (homologous and heterologous) mesenchymal elements in different proportions. UCSs predominantly metastasize as carcinomas and they are associated with a poor prognosis. Although stage is a consistent prognostic factor, the significance of several histopathological features, such as myometrial invasion, lymphovascular space involvement, type of carcinomatous component, extent of the sarcomatous component, and the presence of heterologous elements, remains controversial and probably differs among different stages. Although the diagnosis of UCS is not difficult in most cases, the differential diagnosis may include entities such as undifferentiated or dedifferentiated carcinoma, endometrioid adenocarcinoma with spindle cell elements, sarcomatous overgrowth in a low-grade müllerian adenosarcoma, and pure malignant mesenchymal tumors. Genetic and molecular studies have confirmed the clonal origin of most UCSs and have shown these tumors to be similar to those observed in high-grade/nonendometrioid carcinomas, with p53 mutations being the most common molecular alteration. Finally, from a biological standpoint, the process by which epithelial malignant cells of UCS transdifferentiate to malignant mesenchymal cells could be considered a true example of epithelial mesenchymal transition in human neoplasias.Seminars in Diagnostic Pathology 11/2010; 27(4):274-86. DOI:10.1053/j.semdp.2010.09.005 · 1.80 Impact Factor
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ABSTRACT: (1) To determine the significance of positive peritoneal cytology and pelvic versus para-aortic lymph node involvement in uterine carcinosarcoma. (2) To evaluate the impact of isolated retroperitoneal lymph node involvement (IIIC-N) versus retroperitoneal lymph node involvement plus other evidence of extrauterine disease spread (IIIC-N+) on survival in patients with stage IIIC uterine carcinosarcoma. Data were extracted from the Surveillance, Epidemiology, and End Results database between 1988 and 2005. Statistical analysis used χ, Kaplan-Meier method, and Cox proportional hazards model. A total of 690 women were identified. When comparing overall survival between patients with disease spread to uterine serosa and/or adnexa and those with positive peritoneal cytology, there was no significant difference (25.4% vs 15.5%, P = 0.2). However, although the 5-year overall survival was comparable between patients with positive pelvic lymph nodes and those with positive para-aortic lymph nodes (22.1% vs 25.4%, P = 1.0), it was significantly worse in stage IIIC-N(+) compared to stage IIIC-N patients (15.0% vs 33.4%, P < 0.001). Only patient's age (P < 0.001), race (P = 0.03), stage (P < 0.03), and lymphadenectomy (P < 0.001) were independent predictors of survival after adjusting for other contributing factors. In addition, the results of unadjusted analysis concerning the survival difference between different stage groups were confirmed on multivariate analysis. Positive peritoneal cytology is associated with poor prognosis in uterine carcinosarcoma, comparable to current International Federation of Gynecology and Obstetrics stage IIIA classification of disease. Although there does not seem to be a significant survival difference between patients with positive pelvic versus those with para-aortic lymph nodes, the prognosis seems to be much worse in patients with stage IIIC uterine carcinosarcoma with other evidence of extrauterine disease spread, suggesting the need for more aggressive therapy.International Journal of Gynecological Cancer 06/2011; 21(9):1606-12. DOI:10.1097/IGC.0b013e31822265ad · 1.95 Impact Factor