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Cancers of the small and large bowel originate differently

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Adenocarcinoma of the small intestine and colorectal cancer have different genetic pathways, suggests a molecular study from Oxford. Much rarer than colorectal cancers, cancers of the small intestine are difficult to diagnose and have a poor prognosis. They tend to be adenocarcinomas and are similar to colorectal cancers. So comparing the genetic pathways of each might indicate whether the small intestine is naturally resistant to cancer or might give some clues to clinically significant differences.

Using PCR and gene sequencing on DNA extracted from paraffin sections and immunohistochemical staining of sections with monoclonal antibodies, the researchers looked for particular genes and proteins in the progression to colorectal cancer in 21 non-familial, non-ampullary primary adenocarcinomas of the small intestine. These included mismatch repair genes hMLH1 and hMSH2; adenomatous polyposis coli (APC) gene mutations in the mutation cluster region; and proteins β-catenin, E-cadherin, and p53.

One cancer resulted from replication error. Significantly, no mutations were found in the mutation cluster region of the APC gene, but all cancers were positive for hMLH1 and hMSH2 repair genes. Expression of β-catenin and E-cadherin at the intercellular borders was reduced in 17 and eight of the cancers respectively, and p53 was overexpressed in the nuclei of five cancers.

Lack of mutations in the mutation cluster region of the APC gene in this relatively large study contrasts strongly with colorectal cancer, leading the researchers to conclude that the genetic pathways differ, even though aberrant expression of β-catenin, E-cadherin, and p53 are common features.