Reduced CDH16 expression is linked to poor prognosis in clear cell renal cell carcinoma 16

Objective: Cadherin-16 (CDH16) is a member of the cadherin superfamily which is also termed kidney specific cadherin (ksp-cadherin) because of its preferred expression in the normal kidney where it plays a pivotal role in tubulus formation during embryonal development. However, little is known about the prognostic role of CDH16 in renal cell carcinomas. Methods and material: CDH16 protein was analyzed by immunohistochemistry in more than 1,300 renal cell carcinomas (RCCs) in a tissue microarray format. Results: A CDH16 positivity was found in 81% of 1,115 interpretable tumors. Staining was weak in 34%, moderate in 32% and strong in 15% of tumors. CDH16 positivity was more common in oncocytomas (99% positive) and chromophobe carcinomas (94%) than in papillary (73%) and clear cell RCCs (82%; P < 0.0001). In clear cell RCC, reduced CDH16 staining was significantly linked to high-grade (P < 0.0001), advanced pT stage (P = 0.0452), distant metastasis (P = 0.0003) as well as to shortened recurrence free (P < 0.0001), overall (P = 0.0002), and tumor specific survival (P = 0.0092). In a multivariate analysis including pT, pN, ISUP grade, and M status, CDH16 expression loss was an independent prognostic parameter for overall (P = 0.0016) and tumor specific survival (P = 0.0218) in clear cell RCC. Unequivocal associations with tumor phenotype and prognosis were not seen in papillary RCC. Conclusion: Our data demonstrate that reduction of CDH16 expression is a strong and potentially clinically useful independent predictor of poor prognosis in clear cell RCC. (C) 2022 The Author(s). Published by Elsevier Inc.