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      Immunohistochemical evaluation of mismatch repair proteins and p53 expression in extrauterine carcinosarcoma/sarcomatoid carcinoma

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          Abstract

          Introduction

          Carcinosarcoma (CS) is a tumor with components: epithelial (carcinomatous) and mesenchymal (sarcomatous), developing in the mechanism of epithelial-mesenchymal transition. It is known that the p53 defect is a frequent finding in a carcinosarcoma in different anatomical locations, additionally, in a subgroup of uterine CS MMR defect plays a role in the pathogenesis. The aim of this paper was to investigate the frequency of MMR and p53 aberrations in extrauterine CS.

          Material and methods

          Twenty eight extrauterine CS from the lung ( n = 8), breast ( n = 6), head and neck ( n = 5), ovary ( n = 3), urinary bladder ( n = 3), adrenal gland ( n = 1), skin ( n = 1), and stomach ( n = 1) were stained for hMLH1, PMS2, hMSH2, hMSH6 and p53. The pattern of expression was evaluated separately in carcinomatous and sarcomatous component.

          Results

          Immunostainings for hMLH1, PMS2, hMSH2 and hMSH6 were positive in all tumors. p53 defect was observed in 19 out of 28 samples (67.85%). In all cases except one (96.42%) there was a concordance between sarcomatoid and carcinomatous components.

          Conclusions

          MMR deficiency does not seem to play a role in the pathogenesis of extrauterine CS. p53 aberrant expression is frequent and almost always consistent in carcinomatous and sarcomatous component.

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          Most cited references30

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          Mismatch Repair Deficiency, Microsatellite Instability, and Survival : An Exploratory Analysis of the Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) Trial

          Mismatch repair (MMR) deficiency (MMRD) and microsatellite instability (MSI) are prognostic for survival in many cancers and for resistance to fluoropyrimidines in early colon cancer. However, the effect of MMRD and MSI in curatively resected gastric cancer treated with perioperative chemotherapy is unknown.
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            Genomic analyses of gynaecologic carcinosarcomas reveal frequent mutations in chromatin remodelling genes

            Malignant mixed Müllerian tumours, also known as carcinosarcomas, are rare tumours of gynaecological origin. Here we perform whole-exome analyses of 22 tumours using massively parallel sequencing to determine the mutational landscape of this tumour type. On average, we identify 43 mutations per tumour, excluding four cases with a mutator phenotype that harboured inactivating mutations in mismatch repair genes. In addition to mutations in TP53 and KRAS, we identify genetic alterations in chromatin remodelling genes, ARID1A and ARID1B, in histone methyltransferase MLL3, in histone deacetylase modifier SPOP and in chromatin assembly factor BAZ1A, in nearly two thirds of cases. Alterations in genes with potential clinical utility are observed in more than three quarters of the cases and included members of the PI3-kinase and homologous DNA repair pathways. These findings highlight the importance of the dysregulation of chromatin remodelling in carcinosarcoma tumorigenesis and suggest new avenues for personalized therapy.
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              Adrenocortical carcinoma is a lynch syndrome-associated cancer.

              Adrenocortical carcinoma (ACC) is an endocrine malignancy with a poor prognosis. The association of adult-onset ACC with inherited cancer predisposition syndromes is poorly understood. Our study sought to define the prevalence of Lynch syndrome (LS) among patients with ACC.
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                Author and article information

                Journal
                Contemp Oncol (Pozn)
                Contemp Oncol (Pozn)
                WO
                Contemporary Oncology
                Termedia Publishing House
                1428-2526
                1897-4309
                30 March 2020
                2020
                : 24
                : 1
                : 1-4
                Affiliations
                [1 ]Department of Pathomorphology, Medical University of Gdansk, Gdansk, Poland
                [2 ]Department of Paediatrics, Haematology and Oncology, Medical University of Gdansk, Gdansk, Poland
                [3 ]Department of Pulmonology, Medical University of Gdansk, Gdansk, Poland
                [4 ]Diagnostic and Research Center for Molecular BioMedicine, Institute of Pathology, Medical University of Graz, Austria
                [5 ]Department of Pathology, Neuropathology and Molecular Pathology, Medical University of Innsbruck, Austria
                [6 ]Department of Pathology, Medical Faculty, Otto-von-Guericke University Magdeburg, Germany
                [7 ]Department of Pathology, Klinikum Dessau, Dessau, Germany
                Author notes
                Address for correspondence Piotr Czapiewski, MD Department of Pathology, Medical Faculty, Otto-von-Guericke University Magdeburg, Leipzigerstr. 44, Haus 28, D-39120 Magdeburg. e-mail: czapiewskipiotr@ 123456gumed.edu.pl
                Article
                94718
                10.5114/wo.2020.94718
                7265955
                32514231
                e58d896c-e1ea-4bc0-9bd6-149429a56ee3
                Copyright: © 2020 Termedia Sp. z o. o.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License, allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.

                History
                : 30 January 2020
                : 14 March 2020
                Categories
                Original Paper

                carcinosarcoma,p53,mmr
                carcinosarcoma, p53, mmr

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