OBJECTIVE: The risk of development of colorectal carcinoma is elevated in chronic, long-standing ulcerative colitis (UC). The changes in regenerative and immortalizing pathways caused by the inflammatory process, and that have been proved to be carcinogenic in other human tissues, have not been fully and uniformly described. We assayed the expression alterations of regenerative signal receptors and cell-aging inhibitory systems within colonic crypts by considering the histological activity of the disease. METHODS: I-type insulin-like growth factor receptor (IGF1R), hepatocyte growth factor receptor (HGFR), telomerase reverse transcriptase (TERT) and telomerase associated protein (TP-1) expression were evaluated immunohistochemically on biopsy specimens from 11 mild, 11 moderate and 12 severe active inflammation of UC cases and from 10 normal colonic tissue cases. Independent colonic biopsies from 5 healthy and 7 severe UC cases were used for TaqMan real-time RT-PCR validation. RESULTS: In mild inflammation, all observed parameters showed significantly elevated epithelial protein expression (IGF1R: 22.3 +/- 9.46%; HGFR: 35.3 +/- 22.8%; TERT/TP-1: 2.1 +/- 1.87%/2 +/- 1.32%) compared to normal (p < 0.005). In moderately active inflammation, only IGF1R expression was significantly higher (50.2 +/- 8.6%) compared to normal and mild inflammation (p < 0.005). In severe inflammation, all parameters showed decreased epithelial expression; IGF1R showed decreased mRNA expression, while HGFR was overexpressed and TERT showed a decreased tendency. CONCLUSIONS: The epithelial expression of IGF1R, HGFR and TERT/TP-1 is elevated in mildly active UC. This phenomenon may allow the epithelial cells that collected genetic defects during severe inflammatory episodes pathologically to survive and proliferate.
OBJECTIVE: The risk of development of colorectal carcinoma is elevated in chronic, long-standing ulcerative colitis (UC). The changes in regenerative and immortalizing pathways caused by the inflammatory process, and that have been proved to be carcinogenic in other human tissues, have not been fully and uniformly described. We assayed the expression alterations of regenerative signal receptors and cell-aging inhibitory systems within colonic crypts by considering the histological activity of the disease. METHODS: I-type insulin-like growth factor receptor (IGF1R), hepatocyte growth factor receptor (HGFR), telomerase reverse transcriptase (TERT) and telomerase associated protein (TP-1) expression were evaluated immunohistochemically on biopsy specimens from 11 mild, 11 moderate and 12 severe active inflammation of UC cases and from 10 normal colonic tissue cases. Independent colonic biopsies from 5 healthy and 7 severe UC cases were used for TaqMan real-time RT-PCR validation. RESULTS: In mild inflammation, all observed parameters showed significantly elevated epithelial protein expression (IGF1R: 22.3 +/- 9.46%; HGFR: 35.3 +/- 22.8%; TERT/TP-1: 2.1 +/- 1.87%/2 +/- 1.32%) compared to normal (p < 0.005). In moderately active inflammation, only IGF1R expression was significantly higher (50.2 +/- 8.6%) compared to normal and mild inflammation (p < 0.005). In severe inflammation, all parameters showed decreased epithelial expression; IGF1R showed decreased mRNA expression, while HGFR was overexpressed and TERT showed a decreased tendency. CONCLUSIONS: The epithelial expression of IGF1R, HGFR and TERT/TP-1 is elevated in mildly active UC. This phenomenon may allow the epithelial cells that collected genetic defects during severe inflammatory episodes pathologically to survive and proliferate.
Authors: László Herszényi; Ferenc Sipos; Orsolya Galamb; Norbert Solymosi; István Hritz; Pál Miheller; Lajos Berczi; Béla Molnár; Zsolt Tulassay Journal: Pathol Oncol Res Date: 2008-03-18 Impact factor: 3.201