Molecular markers and clinical behavior of uterine carcinosarcomas: focus on the epithelial tumor component

Abstract

Carcinosarcomas (malignant mixed Mü llerian tumors) of the uterus are rare and aggressive malignancies consisting of an epithelial (carcinoma) and a mesenchymal (sarcoma) tumor component and are considered as metaplastic endometrial carcinomas. This study evaluated molecular characteristics and clinical behavior of uterine carcinosarcomas to improve treatment regimens in the future. Immunohistochemical expression of estrogen receptor-a and -b, progesterone receptor-A and -B, MLH1, MSH2, MSH6, PTEN (phosphatase and tensin homolog deleted on chromosome 10), p53, b-catenin and cyclin D1 was determined in 40 uterine carcinosarcomas. Immunostaining was compared between epithelial and mesenchymal tumor components. To determine the prognostic role of the epithelial component, clinicopathological data and survival were compared between patients with endometrioid and non-endometrioid epithelial tumor components. To determine prognosis of carcinosarcomas compared with high-risk endometrial carcinomas, clinicopathological characteristics and survival were compared between these patients. Hormone receptor expression occurred infrequently: estrogen receptor-a (8%) and -b (32%), progesterone receptor-A (0%) and -B (23%), next to b-catenin (4%) and cyclin D1 (7%). PTEN, MLH1, MSH2 and MSH6 mutations occurred in 39%, 33%, 22% and 21%, respectively (based on absent immunostaining). Overexpression of p53 was observed in 38%. Expression patterns of p53, MSH2 and MSH6 corresponded between epithelial and mesenchymal tumor components. In our cohort, the epithelial component caused the majority of metastases (72%) and vascular invasion (70%). Survival tended to be worse for patients with a non-endometrioid epithelial component compared with an endometrioid epithelial component (5-year survival: 26% and 55%, respectively). Survival was worse for patients with uterine carcinosarcomas compared with high-risk endometrial carcinomas (grade 3 endometrioid and non-endometrioid); 5-year survival rates: 42%, 77% and 57%, respectively. Our results support the monoclonal origin of uterine carcinosarcomas. The epithelial component determines prognosis by causing the majority of metastases and vascular invasion. To improve prognosis, treatment should focus on the epithelial tumor component of uterine carcinosarcomas. Modern Pathology (2011Pathology ( ) 24, 1368Pathology ( -1379 doi:10.1038/modpathol.2011; published online 13 May 2011Keywords: carcinogenesis; clinical behavior; epithelial component; immunohistochemistry; uterine carcinosarcomas Uterine carcinosarcomas (malignant mixed Mü llerian tumors) are rare malignancies of the female genital tract, accounting for 1-5% of uterine malignancies. 1,2 Microscopically, carcinosarcomas consist of two histological malignant components: an epithelial (carcinoma) and a mesenchymal (sarcoma) component. The epithelial component is usually a

A practical approach to the diagnosis of mixed epithelial and mesenchymal tumours of the uterus

“…14 There is also experimental evidence that most carcinosarcomas are monoclonal neoplasms rather than representing collision tumours. 15,16 p53 expression is usually concordant between the epithelial and mesenchymal components exhibiting a diffuse, null or wild-type pattern of expression, thus suggesting a common lineage for the two components. 16 Occasionally, the sarcomatous component only manifests itself in the metastasis or recurrence of a high-grade endometrial carcinoma.…”

“…Survival is largely dependent on stage, but overall 5-year survival is~35%, being worse than that of other 'high-grade' endometrial carcinomas. 15 There is some evidence that behaviour is worse when the epithelial component comprises non-endometrioid (serous, clear cell or undifferentiated) rather than endometrioid carcinoma. A relatively recent study has shown that in stage I uterine carcinosarcomas, the nature of the mesenchymal component is a powerful prognostic indicator; those tumours with heterologous elements having a significantly worse prognosis than those with only homologous mesenchymal component (3-year survival 45 vs 93% for heterologous and homologous neoplasms, respectively).…”

Uterine Malignant Mixed Mullerian Tumour - Revisited In Newer Lights : A Case Report From A Tertiary Care Centre

“…IJBR (2015) 6 (09) www.ssjournals.com It is believed that uterine carcinosarcoma is similar to metaplastic endometrial carcinoma so generally management is based on treatment protocols for high-risk endometrial carcinoma [12] Most commonly followed treatment modality is TAH with BSO, pelvic lymphadenectomy, and para-aortic lymph-node sampling with peritoneal washings [1]. It has been seen that patients having predominant epithelial element show a better response rate to chemotherapy (87.5%) than with patients with predominat sarcomatous component [13].…”

Carcinossarcoma Uterino: Características ClinicoPatológicas e Fatores de Prognóstico

“…Algumas neoplasias poderão ter origem Revista Científica da Ordem dos Médicos www.actamedicaportuguesa.com Luz R, et al Carcinossarcoma uterino, Acta Med Port 2016 Oct;29 (10): [621][622][623][624][625][626][627][628] biclonal e serem tumores de colisão. 3,4 O carcinossarcoma surge mais frequentemente em mulheres com idade avançada (entre os 60 e 70 anos) e de raça negra. Outros fatores de risco identificados são semelhantes aos do carcinoma do endométrio e incluem nuliparidade, obesidade, uso de estrogénios exógenos, uso de tamoxifeno e história de radioterapia pélvica.…”