Introduction: Development of colorectal carcinomas is often caused by dysregulation of the wnt pathway, which plays a fundamental role in cell growth and differentiation. By interacting with beta-catenin, pontin (also known as TIP49a) enhances the transcriptional activity of the LEF-1/TCF/beta-catenin-complex in wnt pathway. The aim of our study was the evaluation of a possible involvement of pontin in the pathogenesis of colorectal carcinoma (CRC).Patients &
Methods: Immunhistochemical staining of pontin and beta-catenin on paraffin slides from colorectal cancer tissue and corresponding normal mucosa of 52 patients with CRC was followed by semiquantitative evaluation by two examiners and western blot analysis of pontin in cancer and normal tissue. Correlation with clinical and pathological data (age, sex, tumor localization, UICC-stage, grading, histological subtype) was done.
Results: Pontin staining was stronger in tumor tissue than in normal tissue in 86,8 % of cases and equal in 13,2 % of cases. In every case more than 76 % of tumor cells showed cytoplasmatic pontin expression. In 29/52 (55,8 %), nuclear staining in tumor tissue was observed (10-80 % of nuclei were stained); whereas there was no nuclear staining in normal tissue. In 32,7 % of cases we found a stronger and in 67,4 % an equal staining of the invasive margin vs. tumor center; in dissociating tumor cells (tumor buds) in 32,6 % a stronger and in 67,4 % of cases an equal staining vs. tumor center was detected. In the subgroup of undifferentiated carcinomas (G4) (n=18), we detected a higher percentage of nuclear expression (66,7 %) vs. 50 % in well to badly differentiated adeno carcinomas. Intensität of staining in undifferentiated carcinomas was at least moderate in 66,7 % of cases vs. 47,1 % in the rest of colon carcinomas. Pontin showed a co-expression with beta-catenin in nuclear staining, in the invasive margin and in tumor buds. In 8 patients a 4-8-fold increase of pontin-expression in tumor tissue vs. normal tissue was detected by western blot.
Conclusion: This is the first study revealing an enhanced pontin expression in human colorectal cancer tissue and the co-expression of pontin with beta-catenin as a key player in wnt signaling. By enhancing the transcriptional activity of the LEF-1/TCF/beta-catenin-transcriptional complex pontin may influence the control of proliferation in colorectal carcinoma and may have oncogenic potential by enhanced expression in colorectal cancer tissue. Pontin is a possible diagnostic marker and therapeutic target for colorectal cancer.