title: 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.
authors.affiliation: Department of Pathology and Medicity Research Laboratory, University of Turku, Kiinamyllynkatu 10, Turku, Finland. tuomas.mirtti@utu.fi
authors.forename: Tuomas
authors.initials: T
authors.lastname: Mirtti
authors.forename: Veli Jukka O
authors.initials: VJ
authors.lastname: Laine
authors.forename: Heikki
authors.initials: H
authors.lastname: Hiekkanen
authors.forename: Saija
authors.initials: S
authors.lastname: Hurme
authors.forename: Outi
authors.initials: O
authors.lastname: Rowe
authors.forename: Timo J
authors.initials: TJ
authors.lastname: Nevalainen
authors.forename: Markku
authors.initials: M
authors.lastname: Kallajoki
authors.forename: Kalle
authors.initials: K
authors.lastname: Alanen
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D002277:Carcinoma / Q000175:diagnosis* / Q000401:mortality* / Q000556:secondary; D018450:Disease Progression; D054501:Group II Phospholipases A2 / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D011467:Prostate / Q000201:enzymology / Q000601:surgery; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000401:mortality* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D019998:Racemases and Epimerases / Q000378:metabolism; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D012333:RNA, Messenger; D054501:Group II Phospholipases A2; D019998:Racemases and Epimerases; C108352:alpha-methylacyl-CoA racemase