Expression of Mismatch Repair Proteins in Merkel Cell Carcinoma

Cancers

卷:13

Klaus Junker¹  HeikoU. Käfferlein²  Kerstin Lang²  Thomas Brüning²  Andrea Tannapfel³  Markus Vogt³  Ulrike Wieland⁴  Steffi Silling⁴  Thomas Meyer⁵  Eggert Stockfleth⁵  Nessr Abu Rached⁵  Marina Skrygan⁵  Thilo Gambichler⁵  Markus Stücker⁵  Laura Susok⁵  JürgenC. Becker⁶ 

[1] Department of Pathology, Klinikum Bremen-Mitte, 28205 Bremen, Germany;

[2] Institute for Prevention and Occupational Medicine of the German Social Accident Insurances (IPA), Ruhr-University Bochum, 44789 Bochum, Germany;

[3] Institute of Pathology, Ruhr-University Bochum, 44789 Bochum, Germany;

[4] National Reference Center for Papilloma- and Polyomaviruses, Institute of Virology, University of Cologne, 50935 Cologne, Germany;

[5] Skin Cancer Center, Department of Dermatology, Ruhr-University Bochum, 44791 Bochum, Germany;

[6] Translational Skin Cancer Research, German Cancer Consortium (DKTK) Partner Site Essen/Düsseldorf, Department of Dermatology, University Duisburg-Essen, 45147 Essen, Germany;

关键词: Merkel cell carcinoma;    Merkel cell polyomavirus;    mismatch repair deficiency;    microsatellite instability;    immune checkpoint inhibitors;    immunotherapy;   

DOI  :  10.3390/cancers13112524

来源: DOAJ

【 摘 要 】

We aimed to assess for the first time the mismatch repair (MMR) protein expression in Merkel cell carcinoma (MCC). Immunohistochemistry was performed for MLH1, MSH2, MSH6, and PMS2 on patients’ tumor tissue (n = 56), including neighbored healthy control tissue. In cases with low-level MMR expression (<10th percentile), we performed multiplex PCR in combination with high-resolution capillary electrophoresis in order to confirm microsatellite instability (MSI). Microscopic evaluation revealed a high median expression for all MMR proteins studied (91.6–96.3%). However, six patients (56/10.7%) had low-level MLH1 expression, six (55/10.9%) had low-level MSH2 expression, five (56/8.9%) had low-level MSH6 expression, and six (54/11.1%) had low-level PMS2 expression. Together, we observed nine (56/16.1%) patients who had low-level MMR expression of at least one protein. Of the patients with low-level MMR expression, MSI evaluation was possible in five cases, revealing one case with high-level MSI. In all MMR proteins assessed, low-level expression was significantly (p = 0.0004 to p < 0.0001) associated with a negative Merkel cell polyomavirus (MCPyV) status. However, the expression profiles of the MMR proteins did not correlate with clinical outcome measures such as disease relapse or death (p > 0.05). MCC appears to be a malignancy characterized by low-level MMR rather than completely deficient MMR in a subset of cases, predominantly affecting MCPyV-negative tumors. Future studies will establish whether this subset of MCC patients respond better to immune checkpoint inhibitor therapy.

【 授权许可】

Unknown