Mismatch repair proteins and microsatellites hit clinical practice

Hereditary nonpolyposis colon cancer (HNPCC) is one of the most common fami lial cancers with characteristic molecular changes that are different from those found in familial adenomatous polyposis (FAP) coli. Genetic mutations in the germline and somatic cells lead to loss of expression of one of the two most commonly involved mismatch repair genes, hMSH2 or hMLH1, and cons equently, to expansion of certain repetitive DNA sequences (microsatellite instability (MSI)). The paper describes a distinct subtype of "HNPCC-like" sporadic colonic carcinoma that can easily be identified by immunohistochem istry. Recognition of this subtype of colonic cancer is important because i t occurs in the younger age group and is associated with better survival, b ut also a five-fold chance of developing a second colorectal carcinoma comp ared to "conventional" colorectal carcinomas.