Cadherin-16 (CDH16) immunohistochemistry: a useful diagnostic tool for renal cell carcinoma and papillary carcinomas of the thyroid.

Cadherin-16 (CDH16) plays a role in the embryonal development in kidney and thyroid. Downregulation of CDH16 RNA was found in papillary carcinomas of the thyroid. To determine the expression of CDH16 in tumors and to assess the diagnostic utility a tissue microarray containing 15,584 samples from 152 different tumor types as well as 608 samples of 76 different normal tissue types was analyzed. A membranous CDH16 immunostaining was predominantly seen in thyroid, kidney, cauda epididymis, and mesonephric remnants. In the thyroid, CDH16 staining was seen in 100% of normal samples, 86% of follicular adenomas, 60% of follicular carcinomas, but only 7% of papillary carcinomas (p < 0.0001). CDH16 positivity was frequent in nephrogenic adenomas (100%), oncocytomas (98%), chromophobe (97%), clear cell (85%), and papillary (76%) renal cell carcinomas (RCCs), various subtypes of carcinoma of the ovary (16-56%), various subtyped of carcinomas of the uterus (18-40%), as well as in various subtypes of neuroendocrine neoplasms (4-26%). Nineteen further tumor entities showed a weak to moderate CDH16 staining in up to 8% of cases. Our data suggest CDH16 as a potential diagnostic marker-as a part of a panel-for the identification of papillary carcinomas of the thyroid, nephrogenic adenomas, and the distinction of renal cell tumors from other neoplasms.

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.