title: High expression of prostate-specific membrane antigen in the tumor-associated neo-vasculature is associated with worse prognosis in squamous cell carcinoma of the oral cavity.
abstract: Prostate-specific membrane antigen (PSMA) is a transmembrane protein expressed in prostate cancer as well as in the neo-vasculature of nonprostatic solid tumors. Here, we determined the expression pattern of PSMA in the vasculature of oral squamous cell carcinoma. Using a previously validated antibody, PSMA staining distribution and cyclooxygenase 2 (COX2) expression status was evaluated in a cohort of patients with squamous cell carcinoma of the oral cavity (n=96) using immunohistochemistry and was correlated with clinicopathological features as well as outcome. Twenty-four (25%) cases showed no detectable PSMA staining, 48 (50%) demonstrated positive immunoreactivity for PSMA in less than 50% of microvessels and 24 (25%) cases showed strong endothelial PSMA expression in more than 50% of tumor-associated microvessels. High endothelial PSMA expression was associated with greatly reduced survival (18.2 vs 77.3 months; P=0.0001) and maintained prognostic significance after adjusting for grade and stage in multivariate analysis (hazard ratio=2.19, P=0.007). Furthermore, we observed a strong association between endothelial PSMA and cancer cell-specific COX2 expression. In conclusion, we provide the first evidence for the prognostic significance of endothelial PSMA expression in oral squamous cell carcinoma and, suggest a potential interaction between arachidonic acid metabolites and endothelial PSMA expression in the tumor neo-vasculature.
authors.affiliation: Division of Medical Biochemistry, Biocenter, Innsbruck Medical University, Innsbruck, Austria. michael.c.haffner@gmail.com
authors.forename: Michael C
authors.initials: MC
authors.lastname: Haffner
authors.forename: Johannes
authors.initials: J
authors.lastname: Laimer
authors.forename: Alcides
authors.initials: A
authors.lastname: Chaux
authors.forename: Georg
authors.initials: G
authors.lastname: Schäfer
authors.forename: Peter
authors.initials: P
authors.lastname: Obrist
authors.forename: Andrea
authors.initials: A
authors.lastname: Brunner
authors.forename: Irmgard E
authors.initials: IE
authors.lastname: Kronberger
authors.forename: Klaus
authors.initials: K
authors.lastname: Laimer
authors.forename: Bora
authors.initials: B
authors.lastname: Gurel
authors.forename: Johann-Benedikt
authors.initials: JB
authors.lastname: Koller
authors.forename: Christof
authors.initials: C
authors.lastname: Seifarth
authors.forename: Bettina
authors.initials: B
authors.lastname: Zelger
authors.forename: Helmut
authors.initials: H
authors.lastname: Klocker
authors.forename: Michael
authors.initials: M
authors.lastname: Rasse
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Doppler
authors.forename: Neil H
authors.initials: NH
authors.lastname: Bander
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000954:Antigens, Surface / Q000378:metabolism*; D001317:Austria / Q000453:epidemiology; D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology*; D005260:Female; D043425:Glutamate Carboxypeptidase II / Q000378:metabolism*; D006801:Humans; D008297:Male; D055806:Microvessels / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000098:blood supply / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D000954:Antigens, Surface; D014408:Biomarkers, Tumor; D011451:Prostaglandin-Endoperoxide Synthases; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II