Endometrial carcinosarcomas have a different prognosis and pattern of spread compared to high-risk epithelial endometrial cancer

Amant, Frédéric; Cadron, Isabelle; Fuso, Luca; Berteloot, Patrick; Jonge, Eric de; Jacomen, G; Robaeys, Johan Van; Neven, Patrick; Moerman, Philippe; Vergote, Ignace

doi:10.1016/j.ygyno.2005.04.027

Cited by 134 publications

(93 citation statements)

References 26 publications

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“…11,12 Evidence is emerging that the epithelial component is the 'driving force' in this tumor type. 5,42 In our population, we observed that the epithelial component was responsible for the majority of metastases (72%) and vascular invasion (70%).…”

Section: Discussionmentioning

confidence: 99%

“…High-risk subtypes of endometrial carcinomas (grade 3 endometrioid and non-endometrioid) show resemblance to the aggressive biological behavior of uterine carcinosarcomas, although prognosis of uterine carcinosarcomas is worse. 11,12 Uterine carcinosarcomas predominantly occur in postmenopausal women and a higher incidence is found among black women compared with white women. 1 Risk factors are similar to endometrial carcinomas: advanced age, obesity, nulliparity and exposure to exogenous estrogen.…”

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confidence: 99%

“…4,13 Prognosis is poor: 5-year survival rates have been reported between 30% and 45.8% in early-stage carcinosarcoma (FIGO stage I/ II) and between 0% and 10% in advanced stage carcinosarcoma (FIGO stage III/IV). 11,12 Until recently, uterine carcinosarcomas were considered as a subtype of uterine sarcomas and were treated correspondingly. However, hardly any improvement of prognosis was observed.…”

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confidence: 99%

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

et al. 2011

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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

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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

et al. 2011

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“…This tumor is relatively uncommon, accounting for only 2%-5% of all uterine cancers, and mostly occurs in elder women. However, MMMT is associated with disproportionally higher mortality rates in comparison with other uterine corporeal malignancies [3,4]. The mesenchymal components often show heterologous differentiation such as rhabdomyosarcoma, chondrosarcoma, and osteosarcoma [5], which is likely due in part to their Müllerian duct (MD) lineage, suggesting a stem cell tumor of the MD.…”

Section: Introductionmentioning

confidence: 99%

CD133+ Cancer Stem Cell–like Cells Derived from Uterine Carcinosarcoma (Malignant Mixed Müllerian Tumor)

et al. 2011

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Cancer stem cells (CSCs) that display tumor-initiating properties have recently been identified. CD133, a surface glycoprotein linked to organ-specific stem cells, has been described as a marker of CSCs in different tumor types. We herein identify and characterize CSCs in human uterine carcinosarcoma (malignant mixed Mü llerian tumor), which is one of the most aggressive and therapy-resistant gynecological malignancies and is considered to be of mesodermal origin. The CD133 1 population was increased in uterine carcinosarcoma, and this population showed biphasic properties in the primary tumor. CD1331 cells predominantly formed spheres in culture and were able to differentiate into mesenchymal lineages. CD1331 cells were more resistant to cisplatin/paclitaxel-induced cytotoxicity in comparison with CD133 2 cells. A real-time polymerase chain reaction analysis of the genes implicated in stem cell maintenance revealed that CD133 1 cells express significantly higher levels of Oct4, Nanog, Sox2, and Bmi1 than CD133 2 cells. Moreover, CD133 1 cells showed a high expression level of Pax2 and Wnt4, which are genes essential for Mü llerian duct formation. These CD133 1 cells form serially transplantable tumors in vivo and the resulting CD1331 tumors replicated the EpCAM, vimentin, and estrogen and progesterone receptor expression of the parent tumor, indicating that CSCs likely differentiated into cells comprising the uterine carcinosarcoma tissue. Moreover, strong CD133 expression in both epithelial and mesenchymal elements in primary tumor demonstrated significant prognostic value. These findings suggest that CD1331 cells have the characteristics of CSCs and Mü llerian mesenchymal progenitors.

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“…[21][22][23][24] Previously, uterine carcinosarcoma was classified as a uterine sarcoma due to histological features and aggressive behavior, but was recently reclassified as an endometrial carcinoma. 23 Similarities between uterine carcinoma and uterine carcinosarcoma have been found in the level of p53 and p27 expression, lymph nodal involvement in malignancies, and risk factors.…”

Section: Molecular Transcriptome Signature Of Uterine Carcinosarcoma mentioning

confidence: 99%

Integrative Analysis of Transcriptome Variation in Uterine Carcinosarcoma and Comparison to Sarcoma and Endometrial Carcinoma

Davidson

Lehmann

Kahles

et al. 2014

Preprint

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Large-scale cancer genomics has made a huge impact onto cancer research. It has allowed the characterization of tumor types in an unprecedented depth. More recent studies target the joint analysis of multiple tumor types to gain insight into similarities and differences on a molecular level. Here we present an analysis of Uterine Carcinosarcoma. The histological similarities to sarcomas and carcinomas warrants an in-depth analysis to Uterine Endometrial Carcinoma as well as Sarcomas and we have used data from The Cancer Genome Atlas to understand transcriptome similarities and diffrences between these tumor types. We have performed a differential transcriptome analysis of Uterine Carinosarcoma to Uterine samples from GTEx to find genes with tumor specifc splicing or expression patterns, which may not only be of interest for a deeper mechanistic understanding of the development and progression of Uterine Carcinosarcoma, but may also be potential tumor markers. Similarities and differences to Sarcomas and Endometrial Carcinomas present new opportunities for the development of new and targeted drug therapies. Finally we have also studied genetic determinants of gene expression and splicing changes and identifed germline variants that explain expression and splicing differences between individuals. This analysis demonstrates the opportunities of integrative comparative analysis between multiple tumor types.

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Endometrial carcinosarcomas have a different prognosis and pattern of spread compared to high-risk epithelial endometrial cancer

Cited by 134 publications

References 26 publications

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

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

CD133+ Cancer Stem Cell–like Cells Derived from Uterine Carcinosarcoma (Malignant Mixed Müllerian Tumor)

Integrative Analysis of Transcriptome Variation in Uterine Carcinosarcoma and Comparison to Sarcoma and Endometrial Carcinoma

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