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CA-IX predicts poor survival in resectable hepatocellular carcinoma

Carbonic anhydrase IX, or CA-IX, expression was a crucial prognostic factor in predicting overall survival and disease-free survival in resectable hepatocellular carcinoma, according to study data.

"The aims of our study were to elucidate the role of CA-IX in vascular invasion, tumor recurrence and HCC progression, to evaluate CA-IX as a predictive biomarker for survival in HCC patients with high tumor stage," the researchers wrote.

Researchers analyzed the expression of 277 unifocal, primary HCC tumors surgically resected from patients enrolled at National Taiwan University Hospital between July 1988 and September 1996. There were 177 males and 50 females, with a mean age of 57.2 years. All patients were followed up to 5 years or until death. Researchers used immunohistochemical staining to screen the tumors to determine the frequency of CA-IX expression and whether there was any clinical and pathological significance of CA-IX expression in HCC.

Overall, CA-IX expression was observed in a small number of tumor cells in 18.9% of patients, focal to heterogeneous in 11% to 50% of tumor cells in 17.6% of patients and diffused in more than 50% of tumor cells in 11.9% of patients, according to the research.

Preliminary analyses showed positive CA-IX expression in HCC was associated with younger age (P = .0446), females (P = .0049) and serum alpha-fetoprotein (AFP) levels greater than 200 ng/mL (P < 1x10-6). CA-IX expression also demonstrated a correlation with tumor size larger than 3 cm (P = .0031) and tumor grades 3 and 4 (P = .0005).

Patients with positive CA-IX expression had a 1.34 times higher rate of tumor recurrence compared with HCC that produced CA-IX-negative tumors (80% vs. 59.8%; P = .001). Among the cohort, 69.9% of patients experienced tumor recurrence within 5 years (158/227). High AFP levels, large tumor size and high tumor stage were independent prognostic factors for disease-free survival (DFS) and OS (P < .05 for all), whereas CA-IX expression was an independent predictor for high tumor stage (P = .0047) and DFS (P = .0456), and a predictor for OS (P = .0762).

Further analysis showed that tumors with CA-IX-positive high-stage HCCs had the lowest DFS and OS rates compared with CA-IX-negative high-stage HCCs.

"Our study revealed that CA-IX expression is an important molecular predictor for postoperative tumor recurrence, and thus a prognostic indicator of unfavorable outcomes, and can be a potential therapeutic target for HCC," the researchers concluded.

Disclosure: The researchers report no relevant financial disclosures.