Abstract

Abstract Background: Prostate-specific membrane antigen (PSMA) is a type II transmembrane glycoprotein with folate hydrolase and neurocarboxypeptidase activity. PSMA has been shown to be consistently expressed in prostatic carcinoma as well as benign prostatic tissue. In addition, PSMA is selectively expressed in the neovasculatrization of multiple non-prostatic solid tumours including breast cancers. Inducible PSMA specific expression on angiogenic vasculator suggests that PSMA participates in neovessel growth in developing tumours. Treatment of solid tumours with anti-angiogenic agents has become an established paradigm in cancer therapy. Our study aims at detecting protein expression level of PSMA in breast cancer patients with or without metastases both in the primary tumour and metastases tissues. Materials and methods: 79 patients with histologically proven breast cancer at the department of Gynecology and Obstetrics at the University of Saarland (Germany) were included. 37 patients showed no sign of lymph node or distant metastases (N0M0). 18 patients showed lymph node metastases (N1M0) and 24 patients were diagnosed with distant metastases occurring on different sites (n=5 liver, n=3 lung, n=5 bone, n=7 brain) (M1). Representative formalin-fixed paraffin-embedded tumour blocks from these specimen were obtained from the department of pathology of University of Saarland. Immunohistochemical staining for PSMA and CD31 was performed on parallel representative tumour sections in each case. Results: An immunohistochemical PSMA expression could be detected in tumour cells and in the neovascularization of breast cancer in 36 patients, 16% (n=25) of these patients with primary breast cancer and 45% (n=11) with metastatic disease. The expression is higher in patients with lymph node metastases (40%) and even higher in patients with distant metastases (45%). The distant metastases themselves showed the highest expression of PSMA (67%) compared to the PSMA expression of lymph nodes (30%) or the primary tumor (45%) in patients with metastatic disease. Besides these results we could show that the PSMA expression significantly depends on the tumor stage of the primary tumor. Patients suffering of early stage breast cancer (T1=12%) showed significantly less PSMA expression than patients with T2 primary tumor (29%) (p=0,008). The PSMA expression in T3 and T4 staged primary breast cancer was elevated up to 75%. Conclusion: This data suggests that PSMA might be involved in the pathogenicity of breast cancer and its metastasis. In addition, PSMA may be an ideal target for diagnostic purposes as well as targeted therapies against metastatic breast cancer. Citation Format: von Heesen A, Kasoha M, Solomayer E-F, Unger C, Bohle R, Zaharia C, Ezziddin S, Juhasz I. Prostate-specific membrane antigen (PSMA) expression in breast cancer and its metastases [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-07-25.

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