Group IIA phospholipase A as a prognostic marker in prostate cancer: relevance to clinicopathological variables and disease-specific mortality.

ABSTRACT

Group IIA Phospholipase A(2) (PLA2-IIA), a key enzyme in arachidonic acid and eicosanoid metabolism, participates in a variety of inflammatory processes but possibly also plays a role in tumor progression in vivo. Our aim was to determine the mRNA and protein expression of PLA2-IIA during prostate cancer progression in localized and metastatic prostate tumors. We evaluated the prognostic significance of PLA2-IIA expression in biochemical recurrence, clinical recurrence and disease-specific survival after surgical treatment. The expression of PLA2-IIA was examined by immunohistochemistry and chromogenic in situ hybridization in tissue microarrays of radical prostatectomy specimens and advanced/metastatic carcinomas. The expression data were analyzed in conjunction with clinical follow-up information and clinicopathological variables. The mRNA and protein expression of PLA2-IIA was significantly increased in Gleason pattern grade 2-4 carcinomas compared with benign prostate (p-values 0.042-0.001). In metastases, the expression was significantly lower than in local cancers (p=0.001). The PLA2-IIA expression correlated positively with Ki-67 and alpha-methylacyl CoA racemase (AMACR) expression. The prognostic evaluation revealed decreased PLA2-IIA protein expression among patients who had died of prostate cancer. In conclusion, PLA2-IIA expression is increased in carcinoma when compared with benign prostate. However, metastatic carcinoma showed decreased expression of PLA2-IIA when compared with primary carcinomas. PLA2-IIA may serve as a marker for highly proliferating, possibly poorly differentiated prostate carcinomas. The protein expression of PLA2-IIA may be diminished in patients who consequently die of prostate cancer.