Abstract 2193: Analysis of oncologic characteristics of penile cancer
Authors: Zhao Bin , Zhang Hushan , Zhang Guoying , Xu Jian , Yang Maolin 
Published: July 2021

Abstract
Background: Penile cancer is a rare malignant tumor characterized by invasive growth and early metastasis. Several risk factors related to penile cancer have been identified, such as human papillomavirus status (HPV), circumcision status, smoking, poor hygiene. Current scientific evidence and guidelines on the management and treatment of penile cancer are rarely updated. In particular, there is insufficient evidence for targeted therapy and immunotherapy for penile cancer. Here, we analyzed features of gene profiling of penile cancer and some biomarkers of immunotherapy such as tumor mutation burden (TMB), PD-L1 expression, and status of microsatellite.
Methods: Totally 26 tumor samples of Chinese patients with penile cancer were consecutively collected in China from January 2018 to June 2020, Next generation sequencing (NGS) was used to detect gene mutation, microsatellite instability (MSI) or microsatellite stable (MSS), and tumor mutational burden (TMB) analyzed by a 733 gene panel by 3D Medicines, a laboratory accredited by College of American Pathologists (CAP) and Clinical Laboratory Improvement Amendments (CLIA). PD-L1 expression detected by using Dako PD-L1 IHC 22C3 pharmDx, Tumor Proportion Score (TPS) was used to determine expression of PD-L1. TPS was arranged into the following intervals: strong positive ≥50%, moderate positive ≥5% and &lt;50%, weak positive ≥1% and &lt;5%, and negative &lt;1%.
Results: Among these 26 samples, 20 samples were available for TMB analysis and MSI/MSS analysis, and 15 samples were available for analysis of PD-L1 expression. The average TMB level of these penile cancer was 7.4 mutants/Mb, and 85% (17/20) of them with TMB level under 10 mutants/Mb. Analysis of PD-L1 expression results showed that 26.7% (4/15) with PD-L1 negative, 6.7% (1/15) weak positive, 53.3% (8/15) moderate positive, 13.3%(2/15) with PD-L1 strong positive. In addition, none of these sample were MSI. Furthermore, NGS results show that a total of 176 gene mutations have been identified in these 26 Chinese patients with penile cancer, and 43.2% (73/176) were germline mutation. The main mutated gene were TP53 (65.4%,17/26), CDKN2A (50.0%,13/26), AKT (46.2%,12/26), FAT1 (38.5%,10/26), PIK3CA/MSH2/POLD1/VEGFA (34.6%, 9/26), BRIP1/MDM2/ATM/XPC/TERT (30.8%,8/26). The top ten of germline mutated genes were AKT (42.3, 11/26), XPA (38.5%,10/26), POLD1 (34.6%, 9/26), ERCC2/TP53/RAC1/MSH2/MSH3/ATM/VEGFA/PRKDC/MGMT/BLM/MDM2/BRIP1/PRSS1/ERCC5 (30.5%,8/26).
Conclusion: Patients with penile cancer have rich spectrum of gene mutations, especially, high percentage of germline mutation was displayed in penile cancer, it may suggest that genetic/Familial high-risk should be put into consideration in the management of penile cancer. What's more, immunotherapy may also have certain potential because of the expressing of PD-L1.
Citation Format: Bin Zhao, Hushan Zhang, Guoying Zhang, Jian Xu, Maolin Yang. Analysis of oncologic characteristics of penile cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2193.