American journal of clinical pathology · 2025
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.
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Tekin Burak, Cheville John C, Lucien Fabrice, McCarthy Michael, Dong Haidong, Kopp Karla J, Torell Nate R, Lavoie Roxane R, Farrell Ava, Jaszewski Brandy L, Smith Carin Y, Jenkins Sarah M, Dasari Surendra, Menon Santosh, Whaley Rumeal D, Boorjian Stephen A, Pagliaro Lance C, Erickson Lori A, Guo Ruifeng, Gupta Sounak
Аннотация
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.
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.