Prognostic significance of DNA repair proteins MLH1, MSH2 and MGMT expression in non-small-cell lung cancer and precursor lesions.
OBJECTIVE
To investigate the role of DNA repair proteins and their prognostic significance in non-small-cell lung cancer (NSCLC).


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.
Cooper
W A
WA
Department of Anatomical Pathology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia. wendy.cooper@email.cs.nsw.gov.au
Kohonen-Corish
M R J
MR
Chan
C
C
Kwun
S Y
SY
McCaughan
B
B
Kennedy
C
C
Sutherland
R L
RL
Lee
C-S
CS
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002278:Carcinoma in Situ / Q000175:diagnosis / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D015254:DNA Modification Methylases / Q000378:metabolism*; D045643:DNA Repair Enzymes / Q000378:metabolism*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D000070956:MutL Proteins; D009363:Neoplasm Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D011379:Prognosis; D015996:Survival Rate; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C088996:PMS1 protein, human; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D000070957:MutL Protein Homolog 1; D000070956:MutL Proteins; D045643:DNA Repair Enzymes