Reduced human mismatch repair protein expression in the development of precancerous skin lesions to squamous cell carcinoma

Loss of human mismatch repair (hMSH2) gene function has been linked to here ditary non-polyposis colorectal cancer (HNPCC). Muir-Torre syndrome (NITS), and sporadic cancers, excluding skin cancers unrelated to MTS. We immunohi stochemically examined 125 squamous cell carcinomas (SCCs) using a monoclon al antibody to the hMSH2 protein and compared the results with those for 10 6 precursor lesions of SCC, consisting of actinic keratosis (AK), Bowenoid type of actinic keratosis (BAK), and Bowen's disease (BOD). In contrast to the homogeneous immunoreactivity of proliferating cells composed of AK, BAK , and BOD, heterogeneous and diminished immunostaining to hMSH2 was observe d in tumor cells of SCCs examined. In addition, two SCCs (2 of 125; 1.6%) a t multiple loci exhibited a complete lack of immunoreaction to hMSH2. Immun ohistochemical staining of hMSH2 was semiquantitatively scored as 0 (0% of total cells examined), 1 (less than 10%), 2 (10-50%), or 3 (more than 50%). Percentage preservation of and average score for hMSH2 expression in norma l, AK, BAK, BOD. and SCC were 56% and 2.06. 100% and 2.80, 94% and 2.88. 83 % and 2.78, 63% and 2.36, respectively. The percentage preservation of and average scores for hMSH2 in AK, BAK, and BOD were significantly higher than those in presumably normal skin (P <0.01). There were no significant diffe rences in the percentage preservation of and average scores for hMSH2 betwe en presumably normal skin and SCC. The score for hMSH2 expression was signi ficantly correlated with score for sun exposure in presumably normal skin o f each lesion (R=0.70). These findings for hMSH2 expression in precursor le sions and SCC suggest that promotion or activation of hMSH2 expression may be induced by the increased DNA damage caused by sun exposure and that dimi nished expression of it might occur according to the transformation from pr ecancerous lesions to SCC.