UICC World Cancer Congress 2006

Objective: Colorectal carcinoma (CRC) is the third most common cancer in Iran with an especially high percentage of tumors observed in young. Mutations in the p53 and K-ras genes and microsatellite instability (MIN) status are well known molecular markers of CRC progression. We screened by PCR and sequencing analysis the DNA binding region of the p53 gene, the K-ras mutational hotspots at codons 12, 13 and 61 and the MIN status in a series of 200 paraffin-embedded CRC cases.

Methods: DNA of 194 cases was successfully analyzed for p53. A total of 88/194 cases were mutated (45%). The frequency of p53 mutations increased with increasing tumor stage. We observed a higher frequency of mutations in the recto-sigmoid compared to proximal tumors (51% vs. 29% P<0.05). MIN was seen in 23% of patients. There was no relation between mutations in K-ras and MIN status while p53 mutations correlated with MIN- status (53% of MIN- cases were mutated in p53 compared to 19% of MIN+ cases).

Results: MIN-/p53+ cases accounted for 42% of the proximal and 33% of the distal CRCs. MIN-/K-ras+ and MIN-/K-ras+/p53+ cases accounted for only 6% of proximal tumors compared to 20% of distal tumors. No genetic alteration was found in one fifth of the cases which were located mainly in the distal colon. Our data suggest that multiple pathways are responsible for the progression of distinct subsets of CRCs in young Iranian patients with a significant difference in molecular alterations between proximal and distal CRCs.