Quantification of MET and hepatocyte growth factor/scatter factor expression in colorectal adenomas, carcinomas and non-neoplastic epithelia by quantitative laser scanning microscopy.
Hepatocyte growth factor (HGF)-MET signalling in cancer biology has been well characterized in multiple organ systems. Numerous investigations have described an up-regulation of c-met mRNA in human colorectal adenomas and carcinomas. However, a quantitative immunohistochemical analysis of MET and HGF protein levels in tumor tissues has not been reported previously. Formalin-fixed and paraffin-embedded tissues from 41 colorectal adenomas and 49 colorectal carcinomas were characterized by immunofluorescent staining using HGF- and MET-specific antibodies. The immunoreactivity was evaluated by confocal laser scanning microscopy, computer-based image analysis and appropriate statistical tests. Normal colorectal mucosa, adenomas and carcinomas exhibited comparable levels of MET and HGF proteins. MET expression in carcinomas, although statistically not significant, demonstrated a tendency to correlate with the grade of differentiation. Correlations of MET and HGF with other clinico-pathological variables including the extent of the mucinous component and the pTNM stage were not observed. The ratio of HGF in carcinoma vs. non-neoplastic tissue was significantly different between high and low carcinoma stage. Alterations of absolute levels of MET and HGF protein during the colorectal adenoma-carcinoma sequence were not significant. The presumed role of MET-HGF interactions in large bowel carcinogenesis may therefore be a result of or depend upon other regulatory factors involved in MET-mediated signalling pathways.
Baldus
Stephan E
SE
Institute of Pathology, University of Duesseldorf, D-40225 Duesseldorf, Germany. stephan.baldus@uni-duesseldorf.de
Kort
Eric J
EJ
Schirmacher
Peter
P
Dienes
Hans P
HP
Resau
James H
JH
D000236:Adenoma / Q000737:chemistry / Q000473:pathology*; D002277:Carcinoma / Q000737:chemistry / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000737:chemistry / Q000473:pathology*; D004848:Epithelium / Q000737:chemistry; D005453:Fluorescence; D017228:Hepatocyte Growth Factor / Q000032:analysis*; D006801:Humans; D018613:Microscopy, Confocal; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D019859:Proto-Oncogene Proteins c-met; D017978:Receptors, Growth Factor / Q000032:analysis*
D011518:Proto-Oncogene Proteins; D017978:Receptors, Growth Factor; D017228:Hepatocyte Growth Factor; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met