Prostate-specific membrane antigen expression in the neovasculature of gastric and colorectal cancers

Haffner, Michael C.; Kronberger, Irmgard E.; Ross, Jeffrey S.; Sheehan, Christine E.; Zitt, Matthias; Mühlmann, Gilbert; Öfner, Dietmar; Zelger, Bettina; Ensinger, Christian; Yang, Ximing J.; Geley, Stephan; Margreiter, Raimund; Bander, Neil H.

doi:10.1016/j.humpath.2009.06.003

« Previous Next »Human Pathology
Volume 40, Issue 12 , Pages 1754-1761, December 2009

Prostate-specific membrane antigen expression in the neovasculature of gastric and colorectal cancers☆

Michael C. Haffner, MD
- Division of Medical Biochemistry, Biocenter, Innsbruck Medical University, A-6020 Innsbruck, Austria
- Department of Urology, Weill Medical College of Cornell University, New York, NY 10065, USA
- Corresponding author. Division of Medical Biochemistry, Biocenter, Innsbruck Medical University, A-6020 Innsbruck, Austria.
- MCH and IEK contributed equally to this work.
Irmgard E. Kronberger, MD
- Department of General and Transplant Surgery, Innsbruck Medical University, A-6020 Innsbruck, Austria
- MCH and IEK contributed equally to this work.
Jeffrey S. Ross, MD
- Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York 12208, USA
Christine E. Sheehan, MD
- Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York 12208, USA
Matthias Zitt, MD
- Department of General and Transplant Surgery, Innsbruck Medical University, A-6020 Innsbruck, Austria
Gilbert Mühlmann, MD
- Department of General and Transplant Surgery, Innsbruck Medical University, A-6020 Innsbruck, Austria
Dietmar Öfner, MD
- Department of General and Transplant Surgery, Innsbruck Medical University, A-6020 Innsbruck, Austria
Bettina Zelger, MD
- Department of Pathology, Innsbruck Medical University, A-6020 Innsbruck, Austria
Christian Ensinger, MD
- Department of Pathology, Innsbruck Medical University, A-6020 Innsbruck, Austria
Ximing J. Yang, MD, PhD
- Department of Pathology and Laboratory Medicine, New York-Presbyterian Hospital, Weill Medical College of Cornell University, New York, NY 10021, USA
Stephan Geley, MD
- Division of Molecular Pathophysiology, Biocenter, Innsbruck Medical University, A-6020 Innsbruck, Austria
Raimund Margreiter, MD
- Department of General and Transplant Surgery, Innsbruck Medical University, A-6020 Innsbruck, Austria
Neil H. Bander, MD
- Department of Urology, Weill Medical College of Cornell University, New York, NY 10065, USA

Received 1 March 2009; received in revised form 6 June 2009; accepted 11 June 2009. published online 28 August 2009.

Summary

Prostate-specific membrane antigen (PSMA), a type II transmembrane metallo-peptidase highly overexpressed in prostate cancer cells, has been studied as a targeting molecule in prostate cancer. Recently, PSMA has also been found to be expressed in the neovasculature of multiple nonprostatic solid tumors. Because of its unique expression pattern limited to tumor-associated endothelial cells, PSMA may also be an interesting molecule for vascular targeting. In this study, PSMA expression was determined by immunohistochemistry in 119 cases of primary gastric adenocarcinoma, 130 cases of primary colorectal adenocarcinoma, and 24 metastasis of colorectal adenocarcinoma. Expression data were correlated with clinicopathologic information. PSMA expression was detected in tumor-associated neovasculature of 79 (66%) of 119 gastric and 110 (85%) of 130 colorectal carcinomas. Furthermore, the neovasculatures of 16 (84%) of 19 liver and 4 (80%) of 5 nodal metastases from colorectal carcinomas were prostate-specific membrane antigen positive. There was a trend for high-grade tumors to higher PSMA expression (Spearman r = 0.18, P = .046) in colorectal cancers. No association between PSMA expression and overall- or disease-free survival was observed in gastric or colorectal cancers. This study provides the first in-depth look at PSMA expression in gastric and colorectal cancer. Because of its highly tumor-restricted expression and its accessibility to targeted therapy, PSMA represents a promising therapeutic and diagnostic target in colorectal and gastric cancer.

Keywords: PSMA, FOLH1, Neoangiogenesis, Tumor endothelial marker, Colon cancer, Gastric cancer, Antiangiogenic therapy, Prognostic factor, Vascular targeting