Uterine Carcinosarcomas - Diagnosis and Management

Denschlag, Dominik; Ulrich, U.

doi:10.1159/000494335

Cited by 51 publications

(44 citation statements)

References 23 publications

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“…The addition of Trastuzumab to chemotherapy is now recommended for the treatment of HER2-positive advanced or recurrent uterine serous carcinomas [63]. Given the clinically aggressive behavior of UCSs and limited treatment options [64], exploring targeting HER2 in this subset of HER2-amplified UCSs may be warranted [65]. Likewise, therapeutic strategies based on synthetic lethality to target tumors with FBXW7 mutations have emerged [66,67]; given the relatively high frequency of FBXW7 mutations in UCSs (30%), further studies testing this potential treatment strategy might be entertained.…”

Section: Discussionmentioning

confidence: 99%

The genetic landscape of metaplastic breast cancers and uterine carcinosarcomas

et al. 2021

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Metaplastic breast carcinoma (MBC) and uterine carcinosarcoma (UCS) are rare aggressive cancers, characterized by an admixture of adenocarcinoma and areas displaying mesenchymal/ sarcomatoid differentiation. We sought to define whether MBCs and UCSs harbor similar patterns of genetic alterations, and whether the different histologic components of MBCs and UCSs are clonally related. Whole-exome sequencing (WES) data from MBCs (n=35) and UCSs (n=57, The Cancer Genome Atlas) were re-analyzed to define somatic genetic alterations, altered signaling pathways, mutational signatures and genomic features of homologous recombination DNA repair deficiency (HRD). In addition, the carcinomatous and sarcomatous components of an additional cohort of MBCs (n=11) and UCSs (n=6) were microdissected separately and subjected to WES, and their clonal relatedness assessed. MBCs and UCSs harbored recurrent genetic alterations affecting TP53, PIK3CA and PTEN, similar patterns of gene copy number alterations, and an enrichment in alterations affecting the epithelial-to-mesenchymal transition (EMT)-related Wnt and Notch signaling pathways. Differences were observed, however, including FAT3 and FAT1 somatic mutations, which were significantly more common in MBCs than UCSs, and conversely, UCSs significantly more frequently harbored somatic mutations affecting FBXW7 and PPP2R1A as well as HER2 amplification than MBCs. Genomic features of HRD and bi-allelic alterations affecting bona fide HRD-related genes were found to be more prevalent in MBCs than in UCSs. The distinct histologic components of MBCs and UCSs were clonally related in all cases, with the sarcoma component likely stemming from a minor subclone of the carcinoma component in the samples with interpretable chronology of clonal evolution. Despite the similar histologic features and pathways affected by genetic alterations, UCSs differ from MBCs on the basis of FBXW7 and PPP2R1A mutations, HER2 amplification and lack of HRD, supporting the notion that these entities are more than mere phenocopies of the same tumor type in different anatomical sites.

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Section: Discussionmentioning

confidence: 99%

The genetic landscape of metaplastic breast cancers and uterine carcinosarcomas

et al. 2021

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“…EC is a common malignant tumor in women, and is one of the three major malignancies of the female reproductive system that seriously affects the quality of life and health of women [21]. Although the prognosis of low-grade EC (grades 1 and 2) is better than that of high-grade EC (grade 3) [22], some patients with low-grade EC still have recurrence and a poor prognosis.…”

Section: Discussionmentioning

confidence: 99%

Construction and Comprehensive Analysis of the Competing Endogenous Rna Network in Endometrial Adenocarcinoma

Feng¹,

Cui²,

Jin³

et al. 2020

Preprint

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Background: Endometrial carcinoma (EC) is one of the most common gynecological malignant tumors. In this study, we constructed gene co-expression networks to identify key modules and hub genes involved in the pathogenesis of EC. Methods: The RNA profiles of adenocarcinoma and non-adenocarcinoma tissues of patients with EC from The Cancer Genome Atlas were analyzed. MicroRNA, mRNA, and long non-coding RNA networks were constructed based on the differentially expressed RNAs between the two tissues. RNAs from the competing endogenous RNA (ceRNA) networks were then used to construct co-expression networks by weighted gene co-expression network analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed by the Database for Annotation, Visualization and Integrated Discovery tool. Results: The MEturquoise module was found to be significantly related to hypertension and the MEbrown module was significantly related to the history of other malignancies. Functional enrichment analysis showed that the MEturquoise module was associated with the GO biological process terms of transcription from RNA polymerase II promoter, positive regulation of male gonad development, endocardial cushion development, and endothelial cell differentiation. The MEbrown module was associated with GO terms DNA binding, epithelial-to-mesenchymal transition, and transcription from RNA polymerase II promoter. A total of 10 hub genes were identified and validated at transcriptional and translational levels. Conclusions: The identified ceRNAs may play a critical role in the progression and metastasis of EC and are thus candidate therapeutic targets and potential prognostic biomarkers. The two modules constructed further provide a useful reference that will advance understanding of the mechanisms of tumorigenesis in EC.

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“…Unlike CHEC, carcinosarcoma often occurs in elderly women and has a high-stage clinical presentation and more aggressive clinical behavior [9]. Moreover, pathologically carcinosarcoma is mostly composed of high-grade adenocarcinomatous and sarcomatous components with increased nuclear atypia and mitosis [10]. Also, p53 is diffusely and strongly expressed in adenocarcinoma while it is scattered positive in CHEC [11].…”

Section: Discussionmentioning

confidence: 99%

Corded and hyalinized endometrioid carcinoma: a rare case and review of the literature

Lang

Yuan

et al. 2020

Preprint

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Background Corded and hyalinized endometrioid carcinoma(CHEC) is a rare morphological variation of endometrioid carcinoma(EC) in the endometrium. Reports of CHEC were very limited. We represent the clinical and pathological findings of this rare endometrioid carcinoma in a 26-year-old woman and reviews the literatures updated on CHEC. Case presentation: A 26-year-old woman presented with abnormal vaginal bleeding for 3 months and the initial cervical biopsy revealed a mullerian mixed tumor in another clinic. Abdominopelvic computed tomography revealed a mass in the uterine cavity and cervix, suggesting a malignant tumor. Histologically, the tumor showed a biphasic pattern characterized by an appearance of 2 components, the conventional endometrioid carcinoma component and sex cord-like component with hyalinization. In the areas of sex cord-like elements, the epithelioid and spindle cells were usually seen around the glands, and mostly arranged in cords or trabeculaes, sometimes embedded within a richly hyalinized collagenous or sometimes myxoid matrix. Tumor cells in the sex cord-like region show a different immunohistochemical expression pattern from conventional adenocarcinoma. Cytokeratin(CK) and vimentin are positive in both components, and vimentin shows more diffuse positivity while CK is more restricted and focally expressed in tumor cells in the sex cord-like region. Complete loss of expression of E-cadherin and epithelial membrane antigen(EMA) was seen in tumor cells in the sex cord-like region whereas it was well preserved in the area of conventional adenocarcinoma. Nuclear expression of β-catenin was noted in tumor cells in the sex cord-like region. P53 was focally positive in both components. Based on histological and immunochemical examinations, the patient was diagnosed with CHEC. Conclusions CHEC is not uncommonly mistaken for a wide variety of diseases. It’s of great significance to raise the awareness of CHEC to avoid over-treatment caused by over-diagnosis, especially in young patients and in curettage. We report one case of CHEC in a 26-year-old woman which was misdiagnosed as a mullerian mixed tumor in the initial curettage specimen. The clinicopathologic, light microscopic, immunohistochemical features of this tumor are described and the differential diagnosis is discussed.

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Uterine Carcinosarcomas - Diagnosis and Management

Cited by 51 publications

References 23 publications

The genetic landscape of metaplastic breast cancers and uterine carcinosarcomas

The genetic landscape of metaplastic breast cancers and uterine carcinosarcomas

Construction and Comprehensive Analysis of the Competing Endogenous Rna Network in Endometrial Adenocarcinoma

Corded and hyalinized endometrioid carcinoma: a rare case and review of the literature

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