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

• Published in: Histopathology Vol. 52; no. 5; pp. 613 - 622
• Main Authors: Cooper, W A, Kohonen-Corish, M R J, Chan, C, Kwun, S Y, McCaughan, B, Kennedy, C, Sutherland, R L, Lee, C-S
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.04.2008; Blackwell
• Subjects: Adaptor Proteins, Signal Transducing - metabolism; Adult; Aged; Aged, 80 and over; Biological and medical sciences; 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 mismatch repair proteins; DNA Modification Methylases - metabolism; DNA Repair Enzymes - metabolism; Female; Humans; immunohistochemistry; Investigative techniques, diagnostic techniques (general aspects); Lung Neoplasms - diagnosis; Lung Neoplasms - metabolism; Male; Medical sciences; MGMT; Middle Aged; MLH1; MSH2; MutL Protein Homolog 1; MutL Proteins; Neoplasm Proteins - metabolism; non-small-cell lung cancer; Nuclear Proteins - metabolism; Original; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Pneumology; Prognosis; Survival Rate; Tumor Suppressor Proteins - metabolism; Tumors of the respiratory system and mediastinum; Immunohistochemistry; Prognosis; Lung cancer; non-small cell lung carcinoma; Precursor; DNA repair; Repair gene; Base mismatching; Bronchus disease; Lung disease; Enzyme; Respiratory disease; MGMT; Transferases; Malignant tumor; MLH1; Protein; Methylated-DNA-protein-cysteine S-methyltransferase; Anatomic pathology; Methyltransferases; MSH2; DNA; DNA mismatch repair proteins; Lesion; Cancer; non-small-cell lung cancer
• ISSN: 0309-0167; 1365-2559
• 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.