DIAGNOSTIC UTILITY OF CARBONIC ANHYDRASE IX EXPRESSION IN CLEAR CELL RENAL CELL CARCINOMA: AN IMMUNOHISTOCHEMICAL STUDY

Abstract

Background: Clear cell renal cell carcinoma (CCRCC) is the most prevalent subtype of renal cell carcinoma and is characterized by distinct molecular alterations, particularly involving the von Hippel–Lindau (VHL) gene and hypoxia-inducible factor (HIF) pathway. Although routine histopathology remains the cornerstone of diagnosis, morphological overlap with other renal neoplasms can pose diagnostic challenges. Carbonic anhydrase IX (CAIX), a hypoxia-regulated transmembrane enzyme, is consistently overexpressed in CCRCC and has emerged as a valuable immunohistochemical marker for diagnostic confirmation.

Objectives: The present study aimed to evaluate the diagnostic utility of CAIX expression in clear cell renal cell carcinoma and to assess its association with histopathological parameters.

Materials and Methods: This descriptive, observational immunohistochemical study included 42 cases of histologically diagnosed clear cell renal cell carcinoma obtained from nephrectomy specimens over a period of August 2022 to January 2024 at the Department of Pathology, Yenepoya Medical College. Routine hematoxylin and eosin-stained sections were evaluated for tumour grade, stage, and associated pathological features. Representative tumour sections were subjected to immunohistochemical staining using CAIX antibody (rabbit monoclonal, clone EP161) and scored as negative, weak (1+), moderate (2+), or strong (3+). Associations between CAIX expression and clinicopathological variables were tested using the Chi-square test and Fisher's exact test, with p < 0.05 considered significant.

Results: The study population ranged from 29 to 80 years (mean 57 years) with a male predominance (2.8:1). Most tumours were confined to the kidney and classified as ISUP grade 2. CAIX expression was observed in 100% of cases: 52.3% showed strong (3+) diffuse membranous “box-like” staining, 33.3% moderate (2+) staining, and 14.2% weak (1+) staining. CAIX expression intensity was significantly associated with age group (p = 0.020) and presence of tumour haemorrhage (p = 0.021); no significant association was found with gender, tumour size, lymphovascular invasion, sarcomatous differentiation, necrosis, histological grade, or pathological stage.

Conclusion: Uniform and strong expression of CAIX in clear cell renal cell carcinoma underscores its reliability as a diagnostic immunohistochemical marker. CAIX can serve as a valuable adjunct in confirming CCRCC, particularly in cases with overlapping histomorphological features.