N72: CSTF2T And ACTB Discern Sporadic From FAP-Associated Colon Carcinomas At Various Stages Of Carcinogenesis On The Proteomic Level

T. Gemoll1, A. Masche1, U. J. Roblick1, F. Bader1, A. Unger1, S. Becker2, G. Möslein3, U. Hellmann4, H. Jörnvall5, H. P. Bruch1, G. Auer2, J. K. Habermann1

1 – Department of Surgery, University Hospital Schleswig-Holstein, Campus Lübeck, Germany. 2 – Karolinska Biomic Center, Karolinska  Institutet, Stockholm, Sweden. 3 – Department of Surgery, St. Josefs-Hospital Bochum Linden, Bochum, Germany. 4 – Ludwig Institute of Cancer Research, Uppsala, Sweden. 5 – Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.

 

Aim: 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 letal. Thus, additional sensitive diagnostics are required. We aimed at identifying and validating a protein expression signature in macroscopically unaffected colon mucosa that allows identifying genetic carriers of the FAP-syndrome.

Method: Protein profiling by 2-D gel electrophoresis was performed on 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. Analysis aimed at identifying proteins that were expressed in FAP tissue but not in the corresponding sporadic tissue, comparing particularly FAP associated normal mucosa versus sporadic normal mucosa. Target validation was performed by Western and by immunohistochemistry on clinical samples (n=189), respectively.

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. Comparing three FAP carcinomas with seven sporadic colorectal carcinomas yielded 66 proteins with absence/ presence expression pattern. CSTF2T and ACTB were validated by Western Blot and immunohistochemistry in unaffected colon mucosa of FAP patients.

Conclusion: 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.

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