Carbonic Anhydrase IX Expression Predicts Outcome of Interleukin 2 Therapy for Renal Cancer

Abstract

Purpose: Renal cancer response to interleukin 2 (IL-2) therapy and patient survival has been correlated with tumor histology and carbonic anhydrase IX (CAIX) expression. In an effort to confirm and expand these observations, we examined CAIX expression in pathology specimens from renal cancer patients who had previously received IL-2 therapy. Experimental Design: Paraffin-embedded tissue sections of renal cancer were immunostained with the MN-75 monoclonal antibody to CAIX and expression levels were correlated with histologic findings and clinical outcome. Results:Tissue specimens were obtained from 66 patients; 27 of whom (41%) had responded to IL-2^based therapy. Fifty-eight specimens were assessed as clear cell, with 56, 33, and 4 having alveolar, granular, and papillary features, respectively.Twenty-four (36%), 31 (47%), and11 (17%) were classified into good, intermediate, and poor prognosis groups according to the Upton pathology model. Forty-one specimens (62 %) had high CAIX expression. Twenty-one of 27 (78%) responding patients had high CAIX expressing tumors compared with 20 of 39 (51%) nonresponders (odds ratio, 3.3; P = 0.04). Median survival was prolonged (P = 0.04) and survival >5 years was only seen in high CAIX expressers. In patients with intermediate pathologic prognosis, all nine responders had high CAIX expression versus 11 of 22 nonresponders. A resultant group with good pathologic prognosis alone or with intermediate pathologic prognosis and high CAIX contained 26 of 27 (96%) responders compared with18 of 39 (46%) nonresponders (odds ratio, 30; P < 0.01) and exhibited longer median survival (P < 0.01).Conclusions: CAIX expression seems to be an important predictor of outcome in renal cell carcinoma patients receiving IL-2^based therapy and may enhance prognostic information obtained from pathology specimens.

Carbonic Anhydrase IX is Not a Predictor of Outcomes in Non-Metastatic Clear Cell Renal Cell Carcinoma - A Digital Analysis of Tissue Microarray

“…Strong CA-IX expression in more than 85% of the tumor cells is considered an important prognostic factor, and can predict therapeutic response to interleukin-2 (35,36). Similar findings have been described to other tumors, like colorectal carcinoma (37).…”

Absence of VHL gene alteration and high VEGF expression are associated with tumour aggressiveness and poor survival of renal-cell carcinoma

“…These tumours are generally good prognostic tumours that are likely to be cured by surgery or that could be potentially good candidates for immunotherapy in case of metastases. Carbonic Anhydrase IX is generally overexpressed in such tumours and CAIX has been proven to be a good selection criteria for response to interleukin-2-based immunotherapy (Atkins et al, 2005;Patard et al, 2008b). Tumours with VHL alterations and high VEGF levels (Group 2) probably reflect additional molecular events following initial VHL alteration.…”

Tumor Biology and Prognostic Factors in Renal Cell Carcinoma

“…Atkins et al [77] expanded this finding in their evaluation of CAIX expression among 66 patients (27 responders and 39 nonresponders) who received IL-2-based therapy. They too noted a correlation between IL-2 response and CAIX staining, demonstrating a twofold higher response rate in patients with high CAIX expression (odds ratio, 3.3; p ϭ .04).…”