Expression of Carbonic Anhydrase-IX and Vascular Endothelial Growth Factor in Renal Cell Carcinoma and their Prognostic Significance

Renal Cell Carcinoma (RCC) is the most common adult renal malignancy. Histopathologically, clear cell RCC accounts for 65-70% of all RCCs. Carbonic Anhydrase-IX (CA-IX) is a transmembrane protein and takes a role in cancer development and progression. A 75-100% clear cell RCCs show CA-IX expression. But this varies with grade and stage of tumour. Vascular Endothelial Growth Factor (VEGF) is responsible for tumour angiogenesis and expressed variedly in RCCs. Both VEGF and CA-IX expression is mediated by Hypoxia Inducible Factor-1α (HIF-1α). Aim: The present study aimed to evaluate the expression of CA-IX and VEGF in respect to different grades and stages of RCC and assessing their prognostic significance. Materials and Methods: This was a cross-sectional, observational study done on 45 histopathogically diagnosed cases of RCC. It was performed in the Department of Pathology, Nil Ratan Sircar Medical College, Kolkata, West Banglore, India over a period of two years (February 2018 to January 2020). Expression of VEGF and CA-IX were studied by immunohistochemistry. Results were analysed in Statistical Package for Social Sciences (SPSS) software (version 16.0) using Pearson Chi-square test. A p-value of <0.05 was regarded as significant. Results: Out of 45 cases of RCC, 34 tumours (32 clear cell carcinoma and two multilocular cystic renal neoplasm of low malignant potential) were evaluated for CA-IX immuno expression. About 25 cases showed CA-IX positivity which inversely associated with grade and stage of RCC (p-value <0.05). The CA-IX had a diagnostic value in detecting clear cell RCC with sensitivity 73.53%, specificity 100% and accuracy 80%. With 28 (62.2%) cases of RCC showed VEGF positivity among which nine were VEGF 1+ and 19 cases VEGF 2+. The VEGF expression showed a positive association with the grade and Tumour-Node-Metastasis (TNM) stage of tumour (p-value <0.05). Finally, authors found a statistically significant inverse association between CA-IX and VEGF expression in RCCs with clear cell morphology including clear cell RCC and multilocular cystic renal neoplasm of low malignant potential (p-value=0.001). Conclusion: High grade RCCs show low expression of CA-IX and strong positivity with VEGF. Both these markers have a prognostic significance. From the therapeutic point of view, VEGF positive tumours, especially inoperable and metastatic cases, may be benefited by anti-VEGF therapy whereas CA-IX positive tumours respond well by treatment with Interleukin-2.