Monteiro Fernando Sabino Marques, Alencar Junior Antonio Machado, da Trindade Karine Martins, Rebelatto Taiane Francieli, Maluf Fernando C, Gazzola Antonia A, Barrios Pablo M, Bellmunt Joaquim, de Jesus Rafaela Gomes, Silva Gyl Eanes Barros, Teixeira Junior Antonio Augusto Lima, Spiess Philippe E, Fay Andre P
Latin American Cooperative Oncology Group (LACOG), Porto Alegre, Brazil.
Hospital Sírio Libanês, Oncology and Hematology Department, Brasilia, Brazil.
Oncologist. 2025 Feb 6;30(2). doi: 10.1093/oncolo/oyae220.
Penile squamous cell carcinoma (PSCC) is a rare malignancy. However, in developing countries the incidence rate is higher. The understanding of molecular alterations is essential for evaluating possible targets for more effective systemic therapies.
We retrospectively collected clinical data of metastatic PSCC (mPSCC) patients who had received at least one prior systemic treatment from 3 Brazilian hospitals. Tumor samples were evaluated using the next-generation sequencing (NGS) Foundation One DX and immunohistochemistry (IHC). The objective was to identify and describe somatic genomic alterations known to be functional or pathogenic and their association with survival outcomes.
Twenty-three patients were identified, 22 and 18 patients had tumor samples analyzed by IHC and NGS, respectively. PD-L1 expression (CPS ≥ 1%) was positive in 14 patients (63.6%). Regarding the genomic alterations, 16 patients (88.9%) had some clinically relevant genomic alterations. TP53, TERT, CDKN2A, PIK3CA, NOTCH1, and CDKN2B loss were identified in 66.7%, 50%, 50%, 33.3%, 27.8%, and 22.2% of the patients, respectively. No MSI or TMB high (≥10 mutations/MB) cases were identified. NOTCH1 mutation was identified only in HPV-negative patients and it was associated with worse OS (yes: 5.5 vs no: 12.8 months, P = .049) and progression-free survival (yes: 5.5 vs no: 11.7 months, P = .032).
This study demonstrated that molecular alterations in mPSCC from developing countries are similar to those from developed countries. Predictive biomarkers for immunotherapy response such as TMB high or MSI were not identified. Specific gene mutations may identify patients with worse prognoses and open new avenues for therapeutic development.
阴茎鳞状细胞癌（PSCC）是一种罕见的恶性肿瘤。然而，在发展中国家其发病率较高。了解分子改变对于评估更有效的全身治疗的可能靶点至关重要。
我们回顾性收集了来自3家巴西医院的接受过至少一次先前全身治疗的转移性PSCC（mPSCC）患者的临床数据。使用下一代测序（NGS）Foundation One DX和免疫组织化学（IHC）对肿瘤样本进行评估。目的是识别和描述已知具有功能或致病性的体细胞基因组改变及其与生存结果的关联。
共纳入23例患者，分别有22例和18例患者的肿瘤样本进行了IHC和NGS分析。14例患者（63.6%）的PD-L1表达（CPS≥1%）为阳性。关于基因组改变，16例患者（88.9%）存在一些临床相关的基因组改变。分别在66.7%、50%、50%、33.3%、27.8%和22.2%的患者中检测到TP53、TERT、CDKN2A、PIK3CA、NOTCH1和CDKN2B缺失。未发现微卫星高度不稳定（MSI）或肿瘤突变负荷高（≥10个突变/百万碱基）的病例。NOTCH1突变仅在HPV阴性患者中发现，且与较差的总生存期（是：5.5个月 vs 否：12.8个月，P = 0.049）和无进展生存期（是：5.5个月 vs 否：11.7个月，P = 0.032）相关。
本研究表明，发展中国家mPSCC的分子改变与发达国家相似。未发现免疫治疗反应的预测生物标志物，如高肿瘤突变负荷或微卫星高度不稳定。特定基因突变可能识别出预后较差的患者，并为治疗发展开辟新途径。
