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

Histopathology. 2008 Apr;52(5):613-22. doi: 10.1111/j.1365-2559.2008.02999.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism*
  • Carcinoma in Situ / diagnosis
  • Carcinoma in Situ / metabolism*
  • Carcinoma, Non-Small-Cell Lung / diagnosis
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Cell Nucleus / metabolism
  • Cell Nucleus / pathology
  • DNA Modification Methylases / metabolism*
  • DNA Repair Enzymes / metabolism*
  • Female
  • Humans
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / metabolism*
  • Male
  • Middle Aged
  • MutL Protein Homolog 1
  • MutL Proteins
  • Neoplasm Proteins / metabolism*
  • Nuclear Proteins / metabolism*
  • Prognosis
  • Survival Rate
  • Tumor Suppressor Proteins / metabolism*


  • Adaptor Proteins, Signal Transducing
  • Biomarkers, Tumor
  • MLH1 protein, human
  • Neoplasm Proteins
  • Nuclear Proteins
  • PMS1 protein, human
  • Tumor Suppressor Proteins
  • DNA Modification Methylases
  • MGMT protein, human
  • MutL Protein Homolog 1
  • MutL Proteins
  • DNA Repair Enzymes