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

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.

Prostate cancer genes associated with TMPRSS2–ERG gene fusion and prognostic of biochemical recurrence in multiple cohorts

“…Although translation of any such prognostic test would require more analysis and validation, not only by reverse transcriptase PCR but also in other independent cohorts, this study contributes to the current body of knowledge with respect to identifying biomarkers with the potential to improve prostate cancer patient management. Furthermore, certain genes that we found prognostic of recurrence, which were not validated in the Minnesota cohort, have previously been linked to prostate cancer progression, such as mucin 1 (Cozzi et al, 2005), which has also been proposed as a candidate for targeted therapy (Li and Cozzi, 2007), and may warrant further consideration as a prognostic biomarker. Figure 3A) is composed of mRNAs replicated as prognostic of recurrence in this experiment and a 596-patient Minnesota experiment (Nakagawa et al, 2008).…”

Prognostic significance of CDX2 and mucin expression in small intestinal adenocarcinoma

“…9 Membrane-associated mucins are involved in epithelial cell-cell interactions, whereas secreted mucins comprise the major macromolecular component of mucus. 10 The expression patterns appear to be relatively cell, tissue, and organ specific, especially those of secreted mucins. 9 Among mucin proteins, MUC1, MUC5AC, and MUC6 have been investigated in various gastrointestinal organs.…”

Expression of MUC1, MUC2, MUC5AC and MUC6 in cholangiocarcinoma: Prognostic impact

“…MUC6 expression has been reported in malignant epithelial tissues of the lung, breast, prostate, pancreas and stomach (25)(26)(27)(28)(29)(30). Previous studies have reported that MUC6 expression is related with tumor progression and metastatic potential in various cancers (25)(26)(27)(28)(29)(30)(31). A few reports on the clinical impact of the expression of MUC6 in CC patients are available (24,32).…”