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Prognostic significance of DNA repair proteins MLH1, MSH2 and MGMT expression in non-small-cell lung cancer and precursor lesions

Abstract

AIMS: To investigate the role of DNA repair proteins and their prognostic significance in non-small-cell lung cancer (NSCLC). METHODS AND RESULTS: A retrospective analysis of 108 cases of stage I-II NSCLC was undertaken. Immunohistochemical expression of DNA repair proteins MLH1, MSH2 and MGMT was assessed using tissue microarrays of paraffin-embedded samples of invasive carcinoma and precursor lesions. Results were analysed in relation to clinicopathological parameters and patient survival. Reduced expression of MLH1 was found in 58.5% of tumours and occurred less frequently in poorly differentiated tumours (P = 0.044) and large cell carcinomas (P = 0.004). MSH2 and MGMT expression was reduced in 18.1% and 77.8% of cases, respectively. There was an inverse relationship between MLH1 and MSH2 expression (P = 0.012). Normal expression of MLH1, MSH2 and MGMT was found in all cases of squamous metaplasia and squamous dysplasia. Only a single case of carcinoma in situ (12.5%) showed reduced MLH1, none showed reduced MSH2 and 25% showed reduced MGMT. Survival analyses showed no prognostic significance based on expression of MLH1 (P = 0.92), MSH2 (P = 0.78) or MGMT (P = 0.57). CONCLUSIONS: Reduction in expression of DNA repair proteins MLH1, MSH2 and MGMT is relatively common in NSCLC, appears to be a late event in the development of invasive malignancy and does not influence survival in this patient cohort.

Type Journal
ISBN 1365-2559 (Electronic)
Authors Cooper, W. A.;Kohonen-Corish, M. R.;Chan, C.;Kwun, S. Y.;McCaughan, B.;Kennedy, C.;Sutherland, R. L.;Lee, C. S. :
Publisher Name HISTOPATHOLOGY
Published Date 2008-01-01 00:00:00
Published Volume 52
Published Issue 5
Published Pages 613-22
URL http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18370958
Status Published In-print
OpenAccess Link https://publications.gimr.garvan.org.au/download.php?2329_10015/08 Cooper Histo.pdf