Demonstration of associations among notch, numb, itch and siah-1 (stem cell factors) expression and their relations with clinicopathological parameters in colorectal adenomas and carcinomas

Colorectal carcinoma is the most frequent tumor of the gastrointestinal system, and ranks 4th among cancer related deaths. Chemotherapy resistant cancer stem cells are considered to be the primary cause of tumor recurrence. Studies aiming to treat cancer by eliminating the resistance caused by cancer stem cell are reported increasingly. One of the most important pathway in the cancer stem cell is the Notch pathway. Abnormal Notch signaling causes cellular self-renewal in carcinogenesis and disruption of regulation of normal stem cells. Notch signaling has been detected in many types of cancer and have been found to be effective in growth, invasion and metastasis of cancer cells. Consequently, Notch signal inactivation has been proposed as a candidate for use in cancer treatment. The expression of Notch, Numb, Itch and Siah-1 were investigated in 50 colorectal carcinomas (CRC), 30 adenomas and 20 normal colonic tissues both by immunohistochemistry and RT-PCR analysis. Colonic adenocarcinoma cases were evaluated for age, sex, localization of tumor, tumor size, tumor grade, pathological stage, pTNM staging, lymph node metastasis, lymphovascular and perineural invasion and clinicopathological parameters. In our study, an inverse correlation between tumor differentiation (p: 0.001) and survival (p: 0.001); and a statistically significant positive correlation between lymph node metastasis (p: 0.001) and stage (p:0.005) were found. According to Spearman correlation test, Notch protein expression in colon adenocarcinomas was positively correlated with Siah, and inversely correlated with Itch and Numb. In conclusion; in colonic carcinomas, compared to normal tissues, Notch and Siah protein expression was found to be increased whereas Numb and Itch protein levels were decreased. Notch was found to be an important pathway in colon cancer formation, and was also found to be associated with increasing aggressiveness of the tumor and bad prognosis. Targeting Notch pathway for treatment of colon cancer is important for evaluation of tumor metastases and prolonging survival Key words: Colorectal carcinoma, Notch, Numb, Itch, Siah, immunohistochemistry.