MUC1 as a Putative Prognostic Marker for Prostate Cancer

MUC1 is expressed on the apical surface of glandular epithelium. With functions including protection, adhesion and signaling, MUC1 has been implicated in prostate cancer. There are many splice variants, the best characterized of which are MUC1/1 and MUC1/2 which are determined by a SNP (rs4072037, 3506G>A). Blood DNA from the general population, BPH, sporadic and hereditary prostate cancer subjects were genotyped for the rs4072037 SNP. G allele frequencies were significantly reduced in hereditary prostate cancer (15%) compared to population, BPH or sporadic prostate cancer samples (27%, 39% and 26% respectively). In addition, the G allele was lost from 3 of 8 heterozygous sporadic prostate tumor samples compared to matched blood DNA. Bioinformatics analysis of MUC1 protein sequences provides insight into differences between the variants which may be functionally relevant. The literature indicates discrepancies between immunohistochemical studies, possibly due to the variety of MUC1 epitopes targeting diverse regions of the molecule. The contradictory findings in cell lines highlight the problem associated with inadequate experimental systems. This is the first report of genetic differences in MUC1 between blood and prostatic cancer tissue. This finding is important as proof of principle, given that many association studies focus on blood DNA rather than on the tumor DNA. As yet, potential functional differences between splice variants has been paid little attention. Antibodies which discriminate between the variants and standardization of methods would help to clarify whether there is a role for MUC1 as a prognostic marker.

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