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

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.

CDH16 protein was analyzed by immunohistochemistry in more than 1,300 renal cell carcinomas (RCCs) in a tissue microarray format.

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.

Our data demonstrate that reduction of CDH16 expression is a strong and potentially clinically useful independent predictor of poor prognosis in clear cell RCC.