[Immunohistochemical expression and microsatellite instability in Lynch syndrome]

Mutation of the mismatch repair genes MLH1 and MSH2 account for the majority of the genetic abnormalities in Lynch syndrome. Immunohistochemical detection of their protein products is becoming an increasingly common method to detect these mutations. The aim of this study was to compare the expression of MLH1 and MSH2 by immunohistochemistry and its relationship with a group of clinical and histological variables in patients with known Lynch syndrome (n=16) and in cohort of young patients (less than 50 years) who did not meet Amsterdam criteria (n=25). The mean age was 40.7 and 64% were women. Conclusive results were obtained in 40 cases (97.6%). Eighteen cases (45%) showed abnormal expression of either MLH1 (11 cases) or MSH2 (6 cases) and both stains (1 case). Alteration of the normal staining pattern was seen more commonly in patients with Lynch syndrome than in the sporadic group (68.7% vs 28%, p=0.01). A significant correlation was obtained between abnormal protein expression and microsatellite instability (MSI): normal expression: 5.9%, lack of expression: 92.3%, p<0.0001. The sensitivity and specificity of the immunohistochemical to predict MSI were 92.3% and 94.1% respectively. Immunohistochemistry and MSI results did not correlate with any histopathological parameter. In conclusion, in our experience abnormal staining of MLH and MSH correlates strongly with the presence of MSI. In addition it appears that in our population a significant proportion of young patients (< 50 years old) demonstrate alterations in the mismatch repair gene products suggesting an important role of these molecules in tumorigenesis.