Expression of mismatch repair proteins in merkel cell carcinoma
| Autor: | Gambichler, Thilo (Prof. Dr. med.), Abu Rached, Nessr (Dr. med.), Tannapfel, Andrea (Prof. Dr. med.), Becker, Jürgen C. (Prof. Dr. med.), Vogt, Markus (Dipl.), Skrygan, Marina (Dr. rer. nat.), Wieland, Ulrike (Prof. Dr. med.), Silling, Steffi (Dr. rer. nat.), Susok, Laura (Dr. rer. nat.), Stücker, Markus (Prof. Dr. med.), Meyer, Thomas, Stockfleth, Eggert (Prof. Dr. med.), Junker, Klaus (Prof. Dr. med.), Käfferlein, Heiko (Dr. rer. nat.), Brüning, Thomas (Prof. Dr. med.), Lang, Kerstin |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities mismatch repair deficiency Medizin nutritional and metabolic diseases Neoplasms. Tumors. Oncology. Including cancer and carcinogens Article digestive system diseases immune checkpoint inhibitors Merkel cell carcinoma Merkel cell polyomavirus microsatellite instability ddc:610 immunotherapy neoplasms RC254-282 |
| Zdroj: | Cancers Cancers, Vol 13, Iss 2524, p 2524 (2021) Volume 13 Issue 11 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|