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

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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.

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Abbreviations

CaP:

prostate cancer

mAbs:

monoclonal antibodies

MRD:

minimal residual disease

PIN:

prostatic intra-epithelial neoplasia

PSA:

prostate-specific antigen

RRP:

radical retro-pubic prostatectomy

SIGLECS:

sialic-acid-binding immunoglobulin superfamily lectins

SMC:

sialomucin complex

TBS:

tris buffered saline

TAA:

tumor-associated antigens

TMA:

tissue microarrays

TURP:

trans-urethral-resection of the prostate

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Authors and Affiliations

  1. Department of Surgery, St George Hospital, Gray Street, 2217, Kogarah, NSW, Australia

    Paul J. Cozzi

  2. Department of Medicine, University of New South Wales, 2052, Kensington, NSW, Australia

    Paul J. Cozzi, Jian Wang, Barry J. Allen, Pamela J. Russell & Yong Li

  3. Center for Experimental Radiation Oncology, Cancer Care Center, St George Hospital, Gray Street, 2217, Kogarah, NSW, Australia

    Jian Wang, Barry J. Allen & Yong Li

  4. Douglass Hanly Moir Pathology, 2113, North Ryde, NSW, Australia

    Warick Delprado

  5. Department of Medical Physics, Medical School, Queen’s Medical Centre, NG7 2UH, Nottingham, United Kingdom

    Alan C. Perkins

  6. Oncology Research Center, Prince of Wales Hospital, Barker Street, 2031, Randwick, NSW, Australia

    Pamela J. Russell

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  1. Paul J. Cozzi
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  2. Jian Wang
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  3. Warick Delprado
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  6. Pamela J. Russell
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  7. Yong Li
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Correspondence to Yong Li.

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Cozzi, P.J., Wang, J., Delprado, W. et al. MUC1, MUC2, MUC4, MUC5AC and MUC6 Expression in the Progression of Prostate Cancer. Clin Exp Metastasis 22, 565–573 (2005). https://doi.org/10.1007/s10585-005-5376-z

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