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

• DOI: 10.1038/modpathol.2012.66
• Publication Date: 2012-03-30T11:42:35Z
• Authors: Michael C Haffner; Johannes Laimer; Alcides Chaux; Georg Schäfer; Peter Obrist; Andrea Brunner; Irmgard E Kronberger; Klaus Laimer; Bora Gurel; Johann-Benedikt K...; Christof Seifarth; Bettina Zelger; Helmut Klocker; Michael Rasse; Wolfgang Doppler; Neil H Bander
• Keywords: Adult; Aged, 80 and over; Glutamate Carboxypeptidase II; Male; Neovascularization, Pathologic; Middle Aged; Prognosis; 3. Good health; 03 medical and health sciences; 0302 clinical medicine; Prostaglandin-Endoperoxide Synthases; Austria; Antigens, Surface; Microvessels; Biomarkers, Tumor; Carcinoma, Squamous Cell; Humans; Female; Mouth Neoplasms; Endothelium, Vascular; Aged; Neoplasm Staging; Retrospective Studies

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.