[Clinicopathological significance of the expression of carbonic anhydrase I and II in human pancreatic cancer].

OBJECTIVE

To explore the clinicopathological significance of the expression of carbonic anhydrase I (CAI) and carbonic anhydrase II (CAII) protein and mRNA levels in pancreatic ductal adenocarcinoma (PDAC).

METHODS

The expression of CAI and CAII protein in 57 pairs of paraffin-embedded PDAC specimens and adjacent non-cancerous pancreatic tissues were detected by immunohistochemistry. The relationship between the protein expression and clinicopathological characters was analyzed. Western blot and quantitative real-time polymerase chain reaction (QRT-PCR) were used to examine the expression of CAI and CAII protein and mRNA levels in 16 paired fresh PDAC specimens, adjacent non-cancerous pancreatic tissues and 3 different differentiated pancreatic cancer cells (PANC-1, BxPC-3 & SW1990).

RESULTS

The expression of CAI protein was higher in PDAC compared with that in paired non-cancerous pancreatic tissues (t = 2.395, P = 0.020), whereas, CAII expression was significantly lower in PDAC than that in paired non-cancerous pancreatic tissues (t = 4.296, P = 0.000). The expression of CAI and CAII protein had a positive correlation with tumor differentiation (χ(2) = 7.557, P = 0.023; χ(2) = 7.822, P = 0.020) and CAI showed a direct negative correlation with vascular invasion (χ(2) = 6.349, P = 0.012). Univariate and multivariate analysis with clinicopathological characters revealed that the CAII expression was an independent prognostic indicator for PDAC patients (P = 0.017; P = 0.011 respectively). No significant difference of CAI mRNA and protein expression existed between PDAC and adjacent normal pancreatic tissues (t = 1.619, P = 0.126; t = 1.352, P = 0.197) as detected by Western blot and QRT-PCR, but the expression of CAII mRNA and protein levels was much lower in PDAC than that in paired non-cancerous pancreatic tissues, respectively (t = 3.360, P = 0.004; t = 2.934, P = 0.010). Moreover, the mRNA and protein expression of CAI and CAII gradually increased with the better differentiation degree of pancreatic cancer cells.

CONCLUSIONS

CAI is up-regulated and CAII down-regulated in PDAC. Both of them are correlated with tumor differentiation. CAII expression is an independent prognostic indicator for PDAC patients.