Role of CAIX Expression in Conventional Renal Cell Carcinomas as a Diagnostic Marker and its Prognostic Importance

Abstract

Significant advances in understanding of the biology of renal cell carcinoma (RCC) have been achieved recently, which led to novel targeted therapies, revolutionising the management of patients with advanced disease. To date, there are no molecular markers which can reliably predict RCC outcome. We investigated whether a novel kidney cancer marker, carbonic anhydrase IX (CAIX), is associated with progression and survival. A retrospective study was done on patients diagnosed with renal cell carcinoma over a period of 5 years. Immunohistochemical analysis using a CAIX monoclonal antibody was performed on paraffin-embedded blocks from patients treated with nephrectomy for clear cell RCC. Patients were segregated into two categories based on CA IX expression as CA IX ≤ 85% and CA IX > 85%. A comparison was made based on the survival (from date of diagnosis) with CA IX expression. Correlation of CA IX expression and TNM staging, nuclear grading, tumour volume and age was statistically studied using Student's t test. The association between survival and CA IX was done using Mann-Whitney test. The association of CA IX with rest of the prognostic variables were analysed using Fisher's exact test. In our study, CA IX expression > 85% had longer survival compared with those with lower expression ≤ 85%. A significant statistical association was seen with CAIX and lymphovascular emboli, major vessel, perinephric fat, renal sinus fat involvement and distant metastasis. CAIX reflects significant changes in tumour biology that predicts clinical outcome and identify high-risk patients for adjuvant immunotherapy and CAIX targeted therapies.

Keywords: CAIX; Clear cell RCC; Hypoxia; Metastasis; Prognosis; Survival.

Fig. 1

a Gross image renal cell carcinoma. b CcRCC, H&E × 100. c Immunohistochemistry: CA IX score 0. d CAIX score 1. e CAIX score 2. f CAIX score 3

Fig. 2

Types of RCC

Fig. 3

Kaplan-Meier survival analysis. The mean in CA-IX > 85% group is 6.930 with 95% confidence interval of (lower bound 6.242 + upper bound 7.618), and the mean in CA-IX ≤ 85% was 5.542 with 95% confidence interval of (lower bound 3.800 + upper bound 7.284). The median value was 7.410. These observations were found to be statistically significant with a p value of 0.049. This observation highlights that in the CA-IX > 85% group, the overall survival period was greater than the CA-IX ≤ 85%