Alterations in Expression of Cadherin–6 and E–Cadherin during Kidney Development and in Renal Cell CarcinomaShimazui T.a,b · Oosterwijk-Wakka J.b · Akaza H.a · Bringuier P.P.b · Ruijter E.c · Debruyne F.M.J.b · Schalken J.A.b · Oosterwijk E.b
aDepartment of Urology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba–City, Ibaraki, Japan; bUrological Research Laboratory, and cDepartment of Pathology, University Hospital Nijmegen, The Netherlands
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Objectives: Cell–cell adhesion mediated by cadherins is tight and stable and preserves tissue integrity. However, during tissue remodeling, e.g., development, adhesion may be modified for morphogenic movement. Similarly, during carcinogenesis, cell–cell adhesion might alter leading to a more aggressive phenotype. Here we describe cadherin expression patterns in developing, adult, and neoplastic kidney.
Methods: Fetal kidneys were obtained from voluntary terminations of pregnancy and 43 renal cell carcinomas (RCC) and normal kidneys were obtained at nephrectomy. Frozen sections of these specimens were stained immunohistochemically using antibodies against E–cadherin (ECD), cadherin–6 (CAD6) and α–catenin (α–cat).
Results: CAD6 was expressed in lower and middle limbs of the S–shaped bodies, structures that will develop into renal proximal tubules, which also express CAD6. Similarly, ECD was expressed in the upper limb of S–shaped bodies, structures which will develop into distal and collecting tubules which also express ECD. Twenty–four out of 43 RCC (55.8%) displayed a CAD6 (+)/ECD (–)/α–cat (+) phenotype. The other RCC had a CAD6 (+)/ECD (+)/α–cat (+) phenotype (10/43, 23.2%), CAD6 (–)/ECD (+)/α–cat (+) phenotype (3/43, 7.0%) or CAD6 (–)/ECD (–)/α–cat (+) phenotype (6/43, 14.0%), respectively. 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, respectively, ECD expression was seen. Survival curves showed that abnormal CAD6 expression correlated with a poor prognosis rather than abnormal ECD expression.
Conclusions: The combination of cadherin expression appeared to be fixed relatively early during kidney organogenesis. Since almost all RCC originate from proximal tubular epithelial cells (CAD6 (+)/ECD (–)/α–cat (+)), only 55.8% of RCC retained the original cadherin phenotype. Alterations in expression of these molecules may be a reflection of the degree of dedifferentiation 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.
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