阴茎鳞癌中无微卫星不稳定和错配修复蛋白表达缺失的证据。

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

机构信息

Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, Germany,

Department of Otorhinolaryngology - Head and Neck Surgery, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, Germany.

出版信息

Pathobiology. 2019;86(2-3):145-151. doi: 10.1159/000495251. Epub 2019 Jan 16.

DOI:10.1159/000495251

PMID:30650417

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.

摘要

目的

微卫星不稳定性（MSI）和错配修复（MMR）系统缺陷被描述为对免疫检查点治疗（PD-1 阻断）有反应的有益肿瘤特征。同时，FDA 批准 PD-1/PD-L1 抑制治疗用于任何显示 MSI 和/或 MMR 系统缺陷的实体瘤。对于阴茎鳞状细胞癌（SCC），目前尚无关于 MSI 频率和 MMR 蛋白表达改变的数据。因此，我们研究了大量阴茎 SCC 中 MSI 状态和 MMR 蛋白的表达。

方法

使用 NCI 共识微卫星不稳定性检测面板的 5 个标志物（BAT25、26、D2S123、D17S250 和 D5S346）分析 105 例存档福尔马林固定、石蜡包埋的阴茎 SCC 组织的 MSI 状态，或在没有代表性非肿瘤组织的情况下，使用经过验证的 5 个拟单核苷酸重复标记物（BAT25、26 和 NR21、24、27）面板。使用免疫组织化学和我们队列中阴茎 SCC 组织微阵列的一部分（n=75）分析 MMR 蛋白 MLH1、MSH2、MSH6 和 PMS2 的表达。