CAIX Immunostaining in Non-neoplastic Renal Diseases.

Abstract

Carbonic anhydrase 9 (CAIX) is a transmembrane metalloenzyme that regulates cellular adhesion, proliferation, and intra/extracellular pH. It is expressed primarily through a hypoxia-inducible factor 1 (HIF-1)-dependent mechanism. Its over-expression is closely related to somatic mutations in the Von Hippel-Lindau (VHL) gene. Studies have shown that it is over-expressed in renal cell carcinoma. In this study, we aimed to assess the value of CAIX immunostaining as an ancillary diagnostic tool in renal malignancies and medical renal diseases. Slides of kidney tumors and medical kidney diseases were selected to evaluate CAIX expression. Intensity and staining patterns of CAIX were independently assessed by two pathologists. Our results showed strong and diffuse box-like membranous staining pattern in the majority of the clear cell renal cell carcinoma (ccRCC) cases (47/59 cases; 94%). A strong, diffuse cup-shaped staining pattern was observed in clear cell papillary RCC. Variable positivity was observed in other RCC (renal cell carcinoma) subtypes. In non-neoplastic renal conditions, the majority of the cases were negative for CAIX, and only a few cases demonstrated patchy non-specific staining. Of note, a single case of transplanted kidney biopsy taken because of delayed graft function showed a focal area of dilated tubules lined by cells with clear cytoplasm and enlarged nuclei with prominent nucleoli. This area showed diffuse membranous staining for CAIX. Two cases of end-stage renal disease showed a focal circumferential membranous staining pattern for CAIX in dilated tubules. The CAIX immunoreactivity observed in these three cases could be indicative of an early-stage renal cell neoplasm and warrants further investigation.