Regeneration associated growth factor receptor and epithelial marker expression in lymphoid aggregates of ulcerative colitis.
OBJECTIVE
Mesenchymal-epithelial transition may have crucial role in mucosal regeneration, hence we assayed epithelial growth factor receptor (EGFR), insulin-like growth factor receptor-1 (IGF1R), hepatocyte-derived growth factor receptor (HGFR), CDX2 and cytokeratin (CK) expression in lymphoid aggregates (LA) of ulcerative colitis (UC).


METHODS
Tissue microarrays (TMAs) made of biopsy samples from 20 mildly, 20 moderately and 20 severely active UC, 12 non-specific colitis (NSC) and 20 healthy colon were prepared, and immunolabelled with anti-EGFR, -IGF1R, -HGFR, -CDX2, -CK antibodies. After virtual microscopic evaluation, one-way ANOVA and correlation analysis were performed. For validation, TaqMan real-time RT-PCR was performed by using RNA from laser microdissected LA from 10 healthy colon and 10 endoscopically active UC biopsies.


RESULTS
The number of LA was in tight positive correlation with the severity of inflammation (r=0.9). The number of EGFR/HGFR positive subepithelial cells was found to be significantly elevated in severe (21.6+/-2.1%/21.3+/-1.9%), moderate (14.3+/-1.7%/14.6+/-1.6%) and mild (7.2+/-1.6%/7.4+/-1.3%) inflammation compared to healthy colon mucosa (2.6+/-1.4%/2.4+/-1.03%) (p < 0.005). Some alterations were found between UC and NSC samples regarding EGFR and HGFR expression. IGF1R immunoreactive cells were only found in a trace number in all cases. Increasing trend of CDX2 and CK positive subepithelial cells was found in active UC, but it was not in significant correlation with the severity of inflammation.


CONCLUSIONS
EGFR and HGFR positive subepithelial cells in LA may be involved in the induction of the regenerative mucosal processes. The presence of CDX2/CK positive subepithelial cells suggests that mesenchymal-to-epithelial transition may be located to lymphoid aggregates.
Sipos
Ferenc
F
2nd Department of Internal Medicine, Semmelweis University, Budapest, Hungary. sipos.ferenc@freemail.hu
Muzes
Györgyi
G
Valcz
Gábor
G
Galamb
Orsolya
O
Tóth
Kinga
K
Leiszter
Katalin
K
Krenács
Tibor
T
Tulassay
Zsolt
Z
Molnár
Béla
B
D000328:Adult; D000704:Analysis of Variance; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D000071616:CDX2 Transcription Factor; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000378:metabolism* / Q000473:pathology; D003113:Colonoscopy; D005260:Female; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D007633:Keratins / Q000378:metabolism; D008221:Lymphoid Tissue / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D012038:Regeneration; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index
D015415:Biomarkers; D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D018398:Homeodomain Proteins; D007633:Keratins; D019859:Proto-Oncogene Proteins c-met; D017526:Receptor, IGF Type 1