Carbonic anhydrase IX (CA9) expression in multiple renal epithelial tumour subtypes

Area of Science:

• Renal pathology
• Oncologic biomarkers
• Immunohistochemistry

Background:

• Renal epithelial neoplasms (RENs) present diagnostic challenges due to overlapping morphology.
• Carbonic anhydrase 9 (CA9) is a known biomarker for clear cell renal cell carcinoma (CCRCC).
• The utility of CA9 across various REN subtypes requires further clarification.

Purpose of the Study:

• To investigate CA9 expression patterns in a spectrum of RENs.
• To assess the reliability of CA9 as a diagnostic biomarker, particularly in differentiating CCRCC from other RENs.
• To evaluate CA9 sensitivity and specificity across different REN subtypes.

Main Methods:

• CA9 immunostaining was performed on 262 RENs, comprising 119 CCRCCs and 143 non-CCRCCs.
• Immunostaining intensity was categorized as negative, rare (1+), focal (2+), or diffuse (3+).
• Expression levels were analyzed across various REN subtypes, including papillary RCC, chromophobe RCC, clear cell tubulopapillary RCC (CCTPRCC), Xp11.2 RCC, and fumarate hydratase-deficient RCC.

Main Results:

• Diffuse CA9 positivity (3+) was observed in 93% of CCRCCs and 100% of CCTPRCCs.
• Papillary RCCs showed variable CA9 expression (67% with 1+/2+), while chromophobe RCCs were mostly negative (93%).
• Focal or rare CA9 expression was noted in a subset of other RENs, including Xp11.2 RCC and fumarate hydratase-deficient RCC; oncocytomas and eosinophilic solid and cystic RCCs were negative.

Conclusions:

• Diffuse CA9 expression demonstrates high sensitivity for CCRCC and CCTPRCC.
• CA9 is not entirely specific, as focal expression can occur in other renal tumor types.
• CA9 findings should be interpreted alongside morphological, immunophenotypic, and clinical data for accurate diagnosis.