Alterations in expression of cadherin-6 and E-cadherin during kidney development and in renal cell carcinoma

Objectives: Cell-cell adhesion mediated by cadherins is tight and stable an d preserves tissue integrity. However, during tissue remodeling, e.g., deve lopment, adhesion may be modified for morphogenic movement. Similarly, duri ng carcinogenesis, cell-cell adhesion might alter leading to a more aggress ive phenotype. Here we describe cadherin expression patterns in developing, adult, and neoplastic kidney. Methods: Fetal kidneys were obtained from voluntary terminations of pregnan cy and 43 renal cell carcinomas (RCC) and normal kidneys were obtained at n ephrectomy. Frozen sections of these specimens were stained immunohistochem ically using antibodies against E-cadherin (ECD), cadherin-6 (CAD6) and alp ha-catenin (alpha-cat). Results: CAD6 was expressed in lower and middle limbs of the S-shaped bodie s, structures that will develop into renal proximal tubules, which also exp ress CAD6. Similarly, ECD was expressed in the upper limb of S-shaped bodie s, structures which will develop into distal and collecting tubules which a lso express ECD. Twenty-four out of 43 RCC (55.8%) displayed a CAD6 (+)/ECD (-)/alpha-cat (+) phenotype. The other RCC had a CAD6 (+)/ECD (+)/alpha-ca t (+) phenotype (10/43, 23.2%), CAD6 (-)/ECD (+)/alpha-cat (+) phenotype (3 /43, 7.0%) or CAD6 (-)/ECD (-)/alpha-cat (+) phenotype (6/43, 14.0%), respe ctively. On the other hand, normal, heterogeneous, or absent expression of CAD6 was seen in 19, 15, and 9 tumors, whereas in 11, 2, and 30 tumors, res pectively, ECD expression was seen. Survival curves showed that abnormal CA D6 expression correlated with a poor prognosis rather than abnormal ECD exp ression. Conclusions: The combination of cadherin expression appeared to be fixed re latively early during kidney organogenesis. Since almost all RCC originate from proximal tubular epithelial cells (CAD6 (+)/ECD (-)/alpha-cat (+)), on ly 55.8% of RCC retained the original cadherin phenotype. Alterations in ex pression of these molecules may be a reflection of the degree of dedifferen tiation from the primary organ. In addition, scoring of expression patterns including heterogeneous expression could be a useful tool to estimate the malignancy potential of the tumor. Copyright (C) 2000 S. Karger AG, Basel.