Ovarian and Uterine Carcinosarcomas A Comparative Analysis of Prognostic Variables and Survival Outcomes
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.
Available from: Emiliano Cocco
- "Carcinosarcomas comprise 2-5% of all uterine malignancies and have an estimated recurrence rate of 40-60% , with approximately 35% of patients having extra-uterine disease at diagnosis. Although surgical debulking is the mainstay of treatment, the high rate of tumor recurrence and a poor median survival of 16-40 months after diagnosis suggest a need for improved adjuvant treatment [5,6]. "
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ABSTRACT: We evaluated the expression of human trophoblastic cell-surface marker (Trop-2) and the potential of hRS7 - a humanized monoclonal anti-Trop-2 antibody - as a therapeutic strategy against treatment-refractory human uterine (UMMT) and ovarian (OMMT) carcinosarcoma cell lines.
Trop-2 expression was evaluated by immunohistochemistry (IHC) in paraffin-embedded tumor tissues, by real-time polymerase-chain-reaction (RT-PCR) and flow-cytometry in cell lines. Sensitivity to hRS7 antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity was tested using 5-hour chromium-release assays against UMMT and OMMT cells.
Trop-2 expression was elevated in 9 of 26 (35%) UMMT and 8 of 14 (57%) OMMT tissues tested by IHC. Positivity for Trop-2 mRNA by RT-PCR and surface expression by flow cytometry were detected in 2 of 4 cell lines, with high positivity noted in OMMT-ARK-2. OMMT-ARK-2 was highly sensitive to hRS7 ADCC (range: 34.7-41.0%; P < 0.001) with negligible cytotoxicity seen in the absence of hRS7 or in the presence of control antibody (range: 1.1-2.5%). Human IgG did not significantly inhibit ADCC while human complement increased, hRS7-mediated-cytotoxicity against OMMT-ARK-2.
Trop-2 is overexpressed in a proportion of UMMT and OMMT, and hRS7 may represent a novel, potentially highly effective treatment option for patients with treatment-refractory carcinosarcomas overexpressing Trop-2.
Available from: PubMed Central
- "For patients with advanced disease, cytoreduction surgery is recommended based on their previous experiences with ovarian and other uterine neoplasms [7, 56]. In 2010, Garg et al. studied this relationship and found that the risk of death decreased 33% in patients that underwent a lymphadenectomy when compared to those that did not . These results are similar to Nemani's results, that reported a median survival of 54 months in patients who underwent a lymphadenectomy (5-year overall survival of 49%) compared to 25 months in those that did not (5-year overall survival of 34%) . "
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ABSTRACT: Uterine carcinosarcomas (MMMT-malignant mixed Müllerian tumours) are highly aggressive, rare, biphasic tumours composed of epithelial and mesenchymal elements believed to arise from a monoclonal origin. While hysterectomy with bilateral salpingo-oophorectomy remains the mainstay treatment, high rates of recurrence and metastases suggest a need for lymphadenectomy and postoperative adjuvant treatment. There are no established consensus guidelines for therapeutic patient management. Though well recognized that it improves locoregional control, the role of radiation in improving overall survival outcomes remains undecided. Although various combinations of chemotherapy have been explored, an optimal therapeutic modality is yet to be determined. As overall survival rates have not improved in thirty years, it is suggested that targeted chemotherapy and/or a multimodality approach may yield better outcomes. This paper provides a summary of the aetiopathogenesis of carcinosarcomas (MMMT) limited to the uterus with special emphasis on the controversies in the management of these patients.
Available from: Darrell R Borger
- "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. "
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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.
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