Mismatch repair proteins and microsatellites hit clinical practice.
Hereditary nonpolyposis colon cancer (HNPCC) is one of the most common familial 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 consequently, 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 immunohistochemistry. Recognition of this subtype of colonic cancer is important because it occurs in the younger age group and is associated with better survival, but also a five-fold chance of developing a second colorectal carcinoma compared to "conventional" colorectal carcinomas.
Stahl
J
J
Department of Anatomical Pathology, School of Medicine, Flinders University, Adelaide, South Australia.
D048868:Adaptor Proteins, Signal Transducing; D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D020137:Base Pair Mismatch / Q000235:genetics*; D002352:Carrier Proteins; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis / Q000235:genetics*; D004273:DNA, Neoplasm / Q000032:analysis; D004268:DNA-Binding Proteins; D003937:Diagnosis, Differential; D006801:Humans; D007150:Immunohistochemistry; D018895:Microsatellite Repeats / Q000235:genetics*; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein