engleski

Rb1 in sporadic colon cancer

Background: Mutations in numerous genes, oncogenes, tumour suppressor and mismatch repair genes are involved in colorectal carcinogenesis. It is considered that one of the gatekeeper genes involved in this process is Rb1. The aim of our study was to evaluate changes in Rb1 at different levels in the cell in order to elucidate its role in colon cancer. Material and methods: Primer specific PCR was used to evaluate the loss of heterozygosity at the two polymorphic loci in 140 samples of normal tissue and corresponding tumour tissue from sporadic colon cancer patients. Rb1 mRNA expression was analyzed in 50 pairs of normal and corresponding tumour tissue samples using real-time PCR method. Rb1 protein expression was analyzed on 50 tumour paraffin sections using immunohistochemistry. Results: Heterozygosity was detected in 63% and 79% of analyzed samples and LOH was observed in 17% and 12% of informative samples for polymorphic markers Rb1.2 and Rb1.20 respectively. Expression of Rb1 mRNA was higher in moderate and poorly differentiated tumours and tumours classified as Dukes' C. Rb1 protein was immunohistochemically positive in 83% of examined tumour samples. The expression of pRb was found higher in moderate and poorly differentiated tumours and it positively correlated with Dukes stage. Conclusions: Our results support the thesis that malignant transformation in colon tissue is a consequence of more than one genetic alteration and suggest that Rb1 plays a role in this multistep process.

Rb1; sporadic colon cancer; LOH; expression

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