Z Gastroenterol 2005; 43 - 118
DOI: 10.1055/s-2005-869765

Elevated epithelial insulin-like growth factor receptor I (IGFR-I) and C-MET (hepatocyte growth factor receptor) expression in mild and moderate ulcerative colitis can enhance the survival of genetically defected epithelial cells

F Sipos 1, E Tihanyi 1, B Molnár 1, Z Tulassay 1
  • 1Semmelweis Egyetem II.sz. Belgyógyászati Klinika

Background: IGFR-I and c-met are known to be involved in regenerative/age-related changes in several human tissues, but their correlation to the epithelial layer is not clear.

Aims: to examine the role of these proteins in ulcerative colitis (UC) considering of the elevated risk of malignant transformation.

Materials and methods: 5µm thick sections of paraffin embedded formalin fixed colonic biopsies from mildly, moderately and severely active UC and normal colon were assayed immunohistochemically to IGFR-I (Chemicon, Mab 1120) and c-met (Santa Cruz, C12) expression. Altogether 80 samples (10 samples per disease group/obsereved parameter) were examined.

Hematoxylin co-staining was done. Samples were evaluated semiquantitatively with light microscope. ANOVA and LSD test were done.

Results: IGFR-I expression was significantly elevated in mild (22.3±9.46%) and moderate (50.2±8.6%), but not in severe UC (6.4±3.66%) compared to normal (7.2±3.15%) (p<0.005). C-met expression was significantly higher in mild UC (35.3±22.8%), but not in moderate (5.8±3.67%), and severe UC (5.9±2.33%) compared to normal (0.7±0.9%) (p<0.005). Several c-met positive subepithelial folliculi were found.

Conclusions: Based on our previous results that the mutant form of p53 oncoprotein showes higher expression in line with the activity of the inflammation in UC, we think that the genetic damage accumulated in the severely active flares of UC can lead to malignant transformation. Epithelial cells containing the damaged p53 gene are continously triggered to proliferate in mild and moderate inflammation by regenerative signals like IGFR-I and c-met, and thus the survival of potentially malignant cell clones are present. The presence of c-met positive folliculi may represent a regenerative pool in the healing phase of UC.