Editor,—The paper by Cawkwell and colleagues ((1999) Gut 45:409–415; OpenUrlAbstract/FREE Full Text) on the utility of hMLH1 and hMSH2 immunostaining in colorectal cancer may mislead the unwary reader just as it misled the author of the accompanying commentary ((1999) Gut 45:325–326.OpenUrlAbstract/FREE Full Text) . Nowhere in their paper do the authors state that their approach will identify all cases of hereditary non-polyposis colorectal cancer (HNPCC). Nor would their method of ascertainment have picked up many HNPCC families. This is evident from the high proportion (83%) of cases with loss of hMLH1 while only four (apparently) of the 49 subjects with one or more RER positive colorectal carcinomas were diagnosed at less than 50 years of age. No subject was actually confirmed as having HNPCC. Yet the commentary states that the test showed that all HNPCC subjects had a deficit of either hMLH1 or hMSH2.

The test will certainly identify all sporadic RER positive or microsatellite instability-high (MSI-H) colorectal cancers in which the promoter region of hMLH1 is hypermethylated.1 We found that 21/23 previously reported sporadic MSI-H cancers2showed loss of hMLH1. One showed loss of hMSH2. This subject …