OVEREXPRESSION OF GROUP-II PHOSPHOLIPASE A(2) IN HUMAN BREAST-CANCER TISSUES IS CLOSELY ASSOCIATED WITH THEIR MALIGNANT POTENCY

Membrane-associated phospholipase A(2) (M-PLA(2)) is an enzyme that hydrolyses the sn-2 fatty acyl ester bond of phosphoglycerides. We measured M-PLA, concentration in tissue extracts from 325 human breast cancers using a specific radioimmunoassay recently developed. Correlation analyses between the tissue concentration of M-PLA(2) and clinicopathological factors showed that the enzyme level was significantly higher in patients with distant metastasis than in those without. In addition, M-PLA(2) concentration was significantly higher in scirrhous carcinoma than in other histological types. No significant association was found between M-PLA(2) concentration and age, menstrual status, tumour size, histological grade, vessel involvement or oestrogen receptor (ER) and progesterone receptor (PR) status. The expression of M-PLA(2) mRNA was examined in a fibroadenoma, a stage IV breast cancer and its metastatic site of skin. Northern blot analysis showed a clear hybridisation band corresponding to M-PLA(2) mRNA in both primary breast cancer and its metastatic site, while the fibroadenoma expressed a faint band corresponding to M-PLA(2) mRNA. Breast cancer patients with high M-PLA(2) concentrations exhibited significantly shorter disease-free and overall survival than those with low M-PLA(2) concentration at the cut-off point of 5 ng 100 mg(-1) protein, which was determined in a separate study. In multivariate analysis, M-PLA(2) was found to be an independent prognostic factor for disease recurrence and death in human breast cancer. The possible significance of M-PLA(2) expression in human breast cancer tissue is discussed.