Article

Clinical & Experimental Metastasis

, Volume 22, Issue 7, pp 565-573

MUC1, MUC2, MUC4, MUC5AC and MUC6 Expression in the Progression of Prostate Cancer

  • Paul J. CozziAffiliated withDepartment of Surgery, St George HospitalDepartment of Medicine, University of New South Wales
  • , Jian WangAffiliated withDepartment of Medicine, University of New South WalesCenter for Experimental Radiation Oncology, Cancer Care Center, St George Hospital
  • , Warick DelpradoAffiliated withDouglass Hanly Moir Pathology
  • , Alan C. PerkinsAffiliated withDepartment of Medical Physics, Medical School, Queen’s Medical Centre
  • , Barry J. AllenAffiliated withDepartment of Medicine, University of New South WalesCenter for Experimental Radiation Oncology, Cancer Care Center, St George Hospital
  • , Pamela J. RussellAffiliated withDepartment of Medicine, University of New South WalesOncology Research Center, Prince of Wales Hospital
  • , Yong LiAffiliated withDepartment of Medicine, University of New South WalesCenter for Experimental Radiation Oncology, Cancer Care Center, St George Hospital Email author 

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Abstract

Molecular changes are vital for the development of prognostic markers and therapeutic modalities of prostate cancer (CaP). There is growing interest in mucins as treatment targets in human malignancies, including CaP. The role of their expression in the progression of CaP is however unclear. We examined the expressions MUC1, MUC2, MUC4, MUC5AC and MUC6 in CaP tissues using tissue microarrays (TMAs) to look for tumor-associated antigens (TAAs) for targeted therapy. In this study, 120 paraffin-embedded specimens were selected from patients who underwent radical retro-pubic prostatectomy (RRP) or trans-urethral-resection of the prostate (TURP) for primary, untreated CaP and 10 matched lymph node metastases. A series of MUC monoclonal antibodies (mAbs) was used on TMAs by standard immunohistochemistry. Our results indicate that the over-expression of MUC1 was detected in 58% of primary CaP tissues and 90% of lymph node metastases but not in normal prostate or benign tissues, while the expression of MUC2, MUC4, MUC5AC and MUC6 was found to be negative in both normal and cancer tissues. Of the MUC1 positive tumors 86% were Gleason grade 7 or higher. Over-expression of MUC1 was found in late stage CaP while MUC2, 4, 5AC and 6 were negative in CaP. MUC1 is a TAA that is highly related to tumor progression in CaP patients. This antigen is ideal for targeted therapy to control micrometastases and hormone refractory disease but additional studies are necessary to assess its usefulness in patient biopsies and CaP bone metastases before clinical trial.

Keywords

human prostate cancer monoclonal antibodies mucins tissue microarray tumor-associated antigen