Biomarkers of response to antibody-drug conjugates (TROP2 and nectin-4) and the immune microenvironment (NKG7, PD-L1, and B7-H3) in penile squamous cell carcinoma.

IF 2.3 4区医学 Q2 PATHOLOGY

American journal of clinical pathology Pub Date : 2025-05-06 DOI:10.1093/ajcp/aqaf022

Burak Tekin, John C Cheville, Fabrice Lucien, Michael McCarthy, Haidong Dong, Karla J Kopp, Nate R Torell, Roxane R Lavoie, Ava Farrell, Brandy L Jaszewski, Carin Y Smith, Sarah M Jenkins, Surendra Dasari, Santosh Menon, Rumeal D Whaley, Stephen A Boorjian, Lance C Pagliaro, Lori A Erickson, Ruifeng Guo, Sounak Gupta

{"title":"Biomarkers of response to antibody-drug conjugates (TROP2 and nectin-4) and the immune microenvironment (NKG7, PD-L1, and B7-H3) in penile squamous cell carcinoma.","authors":"Burak Tekin, John C Cheville, Fabrice Lucien, Michael McCarthy, Haidong Dong, Karla J Kopp, Nate R Torell, Roxane R Lavoie, Ava Farrell, Brandy L Jaszewski, Carin Y Smith, Sarah M Jenkins, Surendra Dasari, Santosh Menon, Rumeal D Whaley, Stephen A Boorjian, Lance C Pagliaro, Lori A Erickson, Ruifeng Guo, Sounak Gupta","doi":"10.1093/ajcp/aqaf022","DOIUrl":null,"url":null,"abstract":"Objectives: We aimed to assess the expression of biomarkers of response to antibody-drug conjugates (TROP2 and nectin-4) and immune microenvironment (NKG7, PD-L1, and B7-H3) in penile squamous cell carcinoma (pSCC).Methods: Our archive was queried for patients who had a penectomy for pSCC between 2000 and 2022. Primary tumors were immunostained for B7-H3 and NKG7, while metastatic specimens were immunostained for TROP2 and nectin-4. Expression of PD-L1, TROP2, and nectin-4 in primary tumors was previously characterized. H-scores (0-300) were used to quantify expression. Associations between biomarkers, tumor-infiltrating lymphocytes (TILs), and clinicopathologic and outcome parameters were evaluated.Results: For both TROP2 and nectin-4, H-scores within the lymph node metastases were higher compared to those within the primary tumors (mean, 264.5 vs 244.8, P = .0003; mean, 170.6 vs 146.7, P = .05, respectively; 33 paired specimens). For B7-H3 (n = 107), 32.7% of the primary tumors had an H-score of more than 0. In 34.8% of the cases, NKG7 expression was observed in 25% to 50% of the TILs. A significant association was noted between TIL density, B7-H3, NKG7, and PD-L1 expression.Conclusions: Therapeutic strategies targeting TROP2 and nectin-4 hold promise for patients with advanced pSCC. The potential of PD-L1, B7-H3, and NKG7 for predicting response to immunomodulatory treatment warrants further research.","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":" ","pages":""},"PeriodicalIF":2.3000,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"American journal of clinical pathology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/ajcp/aqaf022","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PATHOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Objectives: We aimed to assess the expression of biomarkers of response to antibody-drug conjugates (TROP2 and nectin-4) and immune microenvironment (NKG7, PD-L1, and B7-H3) in penile squamous cell carcinoma (pSCC).

Methods: Our archive was queried for patients who had a penectomy for pSCC between 2000 and 2022. Primary tumors were immunostained for B7-H3 and NKG7, while metastatic specimens were immunostained for TROP2 and nectin-4. Expression of PD-L1, TROP2, and nectin-4 in primary tumors was previously characterized. H-scores (0-300) were used to quantify expression. Associations between biomarkers, tumor-infiltrating lymphocytes (TILs), and clinicopathologic and outcome parameters were evaluated.

Results: For both TROP2 and nectin-4, H-scores within the lymph node metastases were higher compared to those within the primary tumors (mean, 264.5 vs 244.8, P = .0003; mean, 170.6 vs 146.7, P = .05, respectively; 33 paired specimens). For B7-H3 (n = 107), 32.7% of the primary tumors had an H-score of more than 0. In 34.8% of the cases, NKG7 expression was observed in 25% to 50% of the TILs. A significant association was noted between TIL density, B7-H3, NKG7, and PD-L1 expression.

Conclusions: Therapeutic strategies targeting TROP2 and nectin-4 hold promise for patients with advanced pSCC. The potential of PD-L1, B7-H3, and NKG7 for predicting response to immunomodulatory treatment warrants further research.

查看原文本刊更多论文

阴茎鳞状细胞癌对抗体-药物偶联物（TROP2和nectin-4）和免疫微环境（NKG7、PD-L1和B7-H3）反应的生物标志物

目的：我们旨在评估抗体-药物偶联物（TROP2和nectin-4）和免疫微环境（NKG7、PD-L1和B7-H3）在阴茎鳞状细胞癌（pSCC）中的表达。方法：我们的档案查询了2000年至2022年间因pSCC进行阴茎切除术的患者。原发肿瘤进行B7-H3和NKG7免疫染色，转移瘤进行TROP2和nectin-4免疫染色。PD-L1、TROP2和nectin-4在原发肿瘤中的表达此前已被证实。h -score（0-300）用于量化表达。评估生物标志物、肿瘤浸润淋巴细胞（til）、临床病理和结局参数之间的关系。结果：对于TROP2和nectin-4，淋巴结转移内的h评分均高于原发肿瘤内的h评分(平均值，264.5 vs 244.8, P = 0.0003；平均，170.6 vs 146.7, P =。05年,分别;33对标本)。对于B7-H3 (n = 107)， 32.7%的原发肿瘤h评分大于0。在34.8%的病例中，25%至50%的til中观察到NKG7表达。TIL密度、B7-H3、NKG7和PD-L1表达之间存在显著关联。结论：针对TROP2和nectin-4的治疗策略对晚期pSCC患者有希望。PD-L1、B7-H3和NKG7在预测免疫调节治疗应答方面的潜力值得进一步研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

American journal of clinical pathology 医学-病理学

CiteScore

7.70

自引率

2.90%

发文量

367

审稿时长

3-6 weeks

期刊介绍： The American Journal of Clinical Pathology (AJCP) is the official journal of the American Society for Clinical Pathology and the Academy of Clinical Laboratory Physicians and Scientists. It is a leading international journal for publication of articles concerning novel anatomic pathology and laboratory medicine observations on human disease. AJCP emphasizes articles that focus on the application of evolving technologies for the diagnosis and characterization of diseases and conditions, as well as those that have a direct link toward improving patient care.