source: Medizinische Congressorganisation Nürnberg
U. J. Roblick, F. G. Bader, A. Unger, A. Ploner, U. Hellman, G. Möslein, S. Becker, H. Jörnvall, G. Auer, H. P. Bruch, J. K. Habermann
Background: Familial adenomatous polyposis (FAP) is an autosomal dominant inherited disease with a germline mutation of the APC gene. In spite of this specific genetic alteration early diagnosis in young patients without polyposis onset and lack of family history can be difficult and finally lethal. Thus, additional sensitive diagnostics are required. We aimed at identifying a protein expression signature in macroscopically unaffected colon mucosa that allows identifying genetic carriers of the FAP-syndrome.
Methods: Protein profiling by 2-D gel electrophoresis was performed on 47 samples obtained from 15 different patients (FAP, n=8; sporadic colorectal cancer, n=7). Analysis was performed for normal mucosa, adenoma, and carcinoma while comparing FAP-associated tissue with the sporadic counterpart. Spot comparison aimed at identifying proteins that were expressed in FAP tissue but not in the corresponding sporadic tissue or visa versa, comparing particularly FAP associated normal mucosa versus sporadic normal mucosa.
Results: A total of 47 proteins were present in all macroscopically unaffected FAP mucosa specimens but absent in sporadic normal mucosa. Comparing FAP polyps with sporadic colonic polyps revealed 49 polypeptides being present in FAP samples but absent in all sporadic polyps. Only one protein showed an opposite expression pattern with high expression in sporadic polyps. Comparing three FAP carcinomas with seven sporadic colorectal carcinomas yielded 66 proteins with absence/ presence expression pattern.
Conclusions: The data obtained demonstrate specific differences of FAP and sporadic colorectal disease on the protein expression level and could help to identify patients with FAP disease already in macroscopically “normal” colorectal mucosa.
University of Schleswig-Holstein, Karolinska Institutet Stockholm, University of Uppsala, St.Josefs-Hospital Bochum Linden