Molecular and immunohistochemical study of APC exon 16 and its possible role in colorectal carcinoma development

Colorectal cancer ranks second as a cause of cancer deaths. Mutations in the adenomatous polyposis coli (APC) gene, especially in exon 16, could contribute to colorectal carcinoma development. This study explored the correlations between APC gene exon 16 variations/expression and colorectal carcinoma progression.

The frequency of APC exon 16 mutation (rs459552) rose significantly with increasing tumor grade. Similarly, although not statistically significant, the percentage of APC positive staining increased with poorer tumor differentiation, rather than declining. Therefore, the APC exon 16 mutation and expression analysis provides insights into colorectal cancer progression, with the rs459552 mutation correlating with grade and may promoting aggression.

In a case-control study, blood samples from 150 colorectal carcinoma patients and 50 healthy volunteers were analyzed by PCR and sequencing for APC exon 16 variations. The APC protein expression on tissue samples was evaluated by immunohistochemistry and statistical analyses were used to examine clinicopathological correlations.

The sequencing analysis revealed a mutation in exon 16 of the APC gene (rs459552) in 36 % of colorectal cancer cases while absent in all non-cancer controls. Subgroup analysis by tumor grade showed higher prevalence of mutant allele in Grade II and Grade III cases, with frequencies reaching 60.0 % and 69.2 %, respectively, compared to a substantially lower prevalence of 29.4 % in Grade I patients. Immunohistochemistry showed no significant correlation between this mutation and APC expression. APC positivity proportions were 25.5 % in Grade I tumors (n = 26/102) versus 17.1 % in Grade II (n = 6/35) and 46.2 % in Grade III (n = 6/13), showing a non-significant trend of reduced positivity in higher grade tumors (p>0.05). Conclusions: The frequency of APC exon 16 mutation (rs459552) rose significantly with increasing tumor grade. Similarly, although not statistically significant, the percentage of APC positive staining increased with poorer tumor differentiation, rather than declining. Therefore, the APC exon 16 mutation and expression analysis provides insights into colorectal cancer progression, with the rs459552 mutation correlating with grade and may promoting aggression.