No Evidence of Microsatellite Instability and Loss of Mismatch-Repair-Protein Expression in Squamous Cell Carcinoma of the Penis

Stoehr, Robert and Wendler, Olaf and Giedl, Johannes and Gaisa, Nadine T. and Richter, Georg and Campean, Valentina and Burger, Maximilian and Wullich, Bernd and Bertz, Simone and Hartmann, Arndt (2019) No Evidence of Microsatellite Instability and Loss of Mismatch-Repair-Protein Expression in Squamous Cell Carcinoma of the Penis. PATHOBIOLOGY, 86 (2-3). pp. 145-151. ISSN 1015-2008, 1423-0291

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Abstract

Objective: Microsatellite instability (MSI) and a defective mismatch repair (MMR) system were described as beneficial tumor features for response to immune checkpoint therapy (PD-1 blockade). Meanwhile, the FDA approved PD-1/PD-L1 inhibition treatment for any solid tumor showing MSI and/or defects in the MMR system. For squamous cell carcinoma (SCC) of the penis, no data on the frequency of MSI and altered MMR protein expression are available to date. Therefore, we investigated the MSI status and the expression of MMR proteins in a large cohort of penile SCCs. Methods: The MSI status of 105 archival formalin-fixed, paraffin-embedded penile SCCs was analyzed using the 5 markers of the NCI consensus panel for MIS testing (BAT25, 26, D2S123, D17S250, and D5S346), or, in cases without representative nontumorous tissue using a validated panel of 5 quasimonomorphic mononucleotide repeat markers (BAT 25, 26 and NR21, 24, 27). The expression of the MMR proteins MLH1, MSH2, MSH6, and PMS2 was analyzed using immunohistochemistry and a tissue microarray of a subset of penile SCCs from our cohort (n = 75). Results: Overall, in 96/105 cases, at least 4 microsatellite markers gave interpretable results. None of the cases showed MSI. Immunohistochemistry for MMR proteins was analyzable in 70/75 cases. All cases showed a regular expression of the MMR proteins. Conclusion: MSI and defects in MMR protein expression are not regular features of penile SCC and might not act as biomarkers for PD-1/PD-L1 blockade therapy in penile carcinoma. (c) 2019 S. Karger AG, Basel

Item Type: Article
Uncontrolled Keywords: QUASIMONOMORPHIC MONONUCLEOTIDE REPEATS; COLORECTAL-CANCER; PD-1 BLOCKADE; REVEALS; BLADDER; TUMORS; Microsatellite instability; Mismatch-repair; Squamous cell carcinoma; Penile cancer; Tissue microarray
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Urologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 21 Apr 2020 08:59
Last Modified: 21 Apr 2020 08:59
URI: https://pred.uni-regensburg.de/id/eprint/27801

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