COM-1 is over-expressed in human colorectal carcinomas

Abstract

21001 Background: COM-1, candidate of metastasis-1, is a primarily nuclear protein thought to play a role in the development and maintenance of metastatic tumours and to have some mitogenic activity. However subsequent investigations have demonstrated a much more diverse role in cancer and cell growth. Here we have investigated the expression and sub-cellular distribution patterns of COM-1 in human colorectal carcinomas. Methods: Carcinoma and normal matched tissues were collected following surgery and frozen for future analysis. Sections of tissue underwent immuno-histochemistry (IHC) staining for COM-1 to determine degree of staining and changes in cellular distribution of the proteins within the tissue. Furthermore, quantitative analysis (quantitative polymerase chain reaction - qPCR) of mRNA levels of COM-1 transcripts was performed to compare levels in normal tissue with those in carcinoma tissues. Statistical analysis was by the Mann-Whitney test. Results: IHC -Normal tissue demonstrated strong nuclear staining for COM-1 protein with little or no cytoplasmic staining. In carcinoma tissue the level of overall staining was found to be much greater, with a greater degree of cytoplasmic staining and little evidence of nuclear staining. qPCR- COM-1 mRNA expression within cells was significantly higher within tumour tissue when compared to normal tissue (Mean 36.7 v 26.5, p=0.003). Moreover, there was a trend in increasing levels of expression and significance of difference between normal tissue and carcinoma tissue with increasing Dukes stage (A p=.52, B p=0.03, C p=0.03) , T-Stage (1 p=1.0, 2 p=0.69, 3 p=0.04, 4 p=0.03), Nodal status (−ve p=0.07, +ve p=0.04 and tumour differentiation (well diff p=0.91, Mod. Diff p= 0.06, Poor. Diff. p= 0.026). Conclusions: COM-1 expression is increased in colorectal tumour tissues when compared to normal mucosa. This is reflected at both the protein and mRNA levels within the cells. In addition there is evidence of dislocated expression and redistribution of COM-1 protein with normal protein expression remaining intra-nuclear however, in tumours COM-1 then becomes cytoplasmic. Aberant over-expression of COM-1 has been identified in other human carcinoma types and has been linked with advanced disease, here we have demonstrated a similar pattern in colorectal carcinomas. No significant financial relationships to disclose.