Colon cancer specific nuclear matrix protein alterations in human colonic adenomatous polyps.
Most colon cancers arise within preexisting adenomatous polyps or adenomas. The slow evolution from the non-invasive premalignant lesion, the adenomatous polyp, to invasive cancer supports a strategy of early detection. Recently, we identified unique nuclear matrix proteins (NMPs) specific for colon cancer (CC2, CC3, CC4, CC5). Most of the NMPs identified are common to all cell types, but several identified NMPs are tissue and cell line specific. The objective of this study is to describe and characterize the NMP profile of premalignant adenomatous colon polyps. Specifically when in the adenoma-carcinoma sequence four specific colon cancer NMPs, previously described, appear. Using two-dimensional (2-D) gel analysis 20 colon polyps (one juvenile polyp, six tubular adenoma (TA), seven tubulovillous adenoma (TVA), six TVA with focal high-grade dysplasia (HGD), were analyzed for the presence of four (CC2, CC3, CC4, CC5) specific NMPs. CC2 was not seen in any of the premalignant polyps. CC5 was present in only two premalignant TVA with HGD and in one TA. CC3 and CC4 were present in most adenomas. None of the NMPs were seen in the juvenile polyp, which is not considered to be a precursor of colon cancer. CC2 and CC5 are NMPs expressed at the junction of an advanced adenoma and invasive colorectal cancer. CC3 and CC4 are expressed earlier in the evolution of adenomatous polyps. Development of an assay to these proteins may serve as a new method for early detection of colorectal cancer.
Brünagel
Gisela
G
Department of Medicine, University of Pittsburgh School of Medicine and University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15232, USA.
Schoen
Robert E
RE
Getzenberg
Robert H
RH
D018256:Adenomatous Polyps / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D007526:Isoelectric Point; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D034521:Nuclear Matrix-Associated Proteins / Q000737:chemistry / Q000378:metabolism*; D016622:Silver Staining
D014408:Biomarkers, Tumor; D034521:Nuclear Matrix-Associated Proteins