MLH1 promoter hypermethylation in uterine carcinosarcoma rarely coexists with TP53 mutation

Michal Kunc; Anna Gabrych; Bartlomiej Rekawiecki; Adam Gorczynski; Sabine Franke; Johannes Haybaeck; Wojciech Biernat; Piotr Czapiewski

doi:10.5114/wo.2019.89635

eISSN: 1897-4309
ISSN: 1428-2526

Contemporary Oncology/Współczesna Onkologia

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4/2019
vol. 23

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abstract:

Original paper

MLH1 promoter hypermethylation in uterine carcinosarcoma rarely coexists with TP53 mutation

Michal Kunc

¹

,

Anna Gabrych

²

,

Bartlomiej Rekawiecki

³

,

Adam Gorczynski

¹

,

Sabine Franke

⁴

,

Johannes Haybaeck

^{4, 5, 6}

,

Wojciech Biernat

¹

,

Piotr Czapiewski

^{1, 4}

Department of Pathomorphology, Medical University of Gdansk, Poland
Department of Paediatrics, Haematology and Oncology, Medical University of Gdansk, Gdansk, Poland
Department of Pulmonology, Medical University of Gdansk, Gdansk, Poland
Institute of Pathology, Otto-von-Guericke University Magdeburg, Germany
Institute of Pathology, Medical University of Graz, Austria
Department of Pathology, Neuropathology and Molecular Pathology, Medical University of Innsbruck, Austria

Contemp Oncol (Pozn) 2019; 23 (4): 202-207

DOI: https://doi.org/10.5114/wo.2019.89635

Online publish date: 2019/11/07

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Introduction
Carcinosarcoma (CS) is an infrequent neoplasm composed of a carcinomatous and a sarcomatous element. Its molecular pathogenesis is poorly understood. In this study, we investigated the disturbances in the immunohistochemical expression of p53 and mismatch repair (MMR) proteins, as well as their molecular background.

Material and methods
The study group consisted of 20 uterine CSs. We analysed their morphology and immunohistochemical expression of hMLH1, hPMS2, hMSH2, MSH6, and p53 as well as the presence of mutations in TP53 and promoter methylation of the hMLH1. Loss of hMLH1 and PMS2 was found in 3/20 tumours. All cases were positive for hMSH2 and hMSH6. The TP53 mutation was detected in 8/19 tumours (42.1%), whereas MLH1 promoter hypermethylation in 4/19 cases (21%), and one case with synchronous aberrations (5%). Agreement between the results of the genetic and immunohistochemical study was moderate for p53 (k = 0.615, p < 0.01) and strong for MLH1 (k = 0.826, p < 0.01).

Results and conclusions
We demonstrated MLH1 promoter hypermethylation in uterine CS, leading to loss of MLH1 immunostaining. Concomitant aberrations of p53 and hMLH1 are infrequent. It is likely that uterine CS may develop in two independent molecular pathways in association with either chromosomal or microsatellite instability.

keywords:

MLH1 promoter hypermethylation in uterine carcinosarcoma rarely coexists with TP53 mutation

Michal Kunc 1 , Anna Gabrych 2 , Bartlomiej Rekawiecki 3 , Adam Gorczynski 1 , Sabine Franke 4 , Johannes Haybaeck 4, 5, 6 , Wojciech Biernat 1 , Piotr Czapiewski 1, 4

carcinosarcoma, mismatch repair proteins, p53, epithelial-mesenchymal transition, uterus

Michal Kunc

¹

,

Anna Gabrych

²

,

Bartlomiej Rekawiecki

³

,

Adam Gorczynski

¹

,

Sabine Franke

⁴

,

Johannes Haybaeck

^{4, 5, 6}

,

Wojciech Biernat

¹

,

Piotr Czapiewski

^{1, 4}