Sporadik kolorektal kanser ve prekürsör lezyonlarda RAS arayolunun değerlendirilmesi
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Date
2012
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Sağlık Bilimleri Enstitüsü
Abstract
In recent years, for metastatic disease, in particular, targeted anti-EGFR therapy is becoming the treatment of choice for colorectal carcinoma. It is crucial to determine the appropriate molecular markers and to select the patients for therapy to achieve the best result. Tumor resistance to the limited targeted therapy agents and the low cost-effectivitiy increase the need to find new molecular targets for therapy. PI3K/AKT/mTOR and MAPK pathway molecules are the most frequently studied potential agents for targeted therapy. In our study, a large series of cases grouped according to the polyp-carcinoma sequence were analysed for molecules involved in MAPK and PI3K pathways using tissue array and immunohistochemistry in order to evaluate their role in the sequence. Our results showed that MEK1 expression was higher in carcinomas compared to polyps in contrast to ERK1 and ERK2. pAKT expression significantly decreased from carcinomas to adenomatous polyps and serrated polyps. There was a significant correlation between the increased expression of AKT and the size of polyps. mTOR expression was higher in adenomatous polyps than in carcinomas and the expression levels increased with the size of polyps.In conclusion, our results suggest that, pAKT, mTOR, MEK1, ERK1 and ERK2 seem to take place in the early stages of colorectal carcinogenesis. These results may have an important impact on the current literature since our study was designed so that both adenomatous and serrated neoplastic sequences were represented by large numbers of cases allowing a thorough evaluation.
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Keywords
Sporadik kolorektal kanser, prekürsör lezyon