DNA mismatch repair genes hMLH1, hMSH2, and hMSH6 are not inactivated in bronchioloalveolar carcinomas of the lung

• Published in: Cancer 2001-12, Vol.92 (11), p.2898-2901
• Main Authors: Aubry, Marie‐Christine, Halling, Kevin C., Myers, Jeffrey L., Tazelaar, Henry D., Yang, Ping, Thibodeau, Stephen N.
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing; Adenocarcinoma, Bronchiolo-Alveolar - metabolism; Aged; Aged, 80 and over; Base Pair Mismatch; Biological and medical sciences; bronchioloalveolar carcinoma; Carrier Proteins; DNA Repair; DNA-Binding Proteins - metabolism; Female; hereditary nonpolyposis colorectal carcinomas; Humans; Immunohistochemistry; Lung Neoplasms - metabolism; Male; Medical sciences; microsatellite instability; Middle Aged; mismatch repair genes; MutL Protein Homolog 1; MutS Homolog 2 Protein; Neoplasm Proteins - metabolism; Nuclear Proteins; Pneumology; Proto-Oncogene Proteins - metabolism; Tumors of the respiratory system and mediastinum
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/1097-0142(20011201)92:11<2898::AID-CNCR10104>3.0.CO;2-Q

BACKGROUND Defective DNA mismatch repair (MMR) appears to be rare in nonsmall cell carcinomas of the lung. Defective DNA MMR results from genetic or epigenetic alterations that inactivate the DNA MMR genes hMLH1 or hMSH2, and rarely hMSH6. The loss of normal DNA MMR is thought to promote tumorigenesis by accelerating the accumulation of mutations in oncogenes and tumor suppressor genes. Inactivation of hMLH1, hMSH2, and hMSH6 is observed as a loss of expression of these proteins by immunohistochemistry. Bronchioloalveolar carcinoma is a subtype of adenocarcinoma with distinctive clinical and pathologic features. MATERIALS AND METHODS. An immunohistochemical study was performed on paraffin embedded sections of 33 bronchioloalveolar carcinomas (20 nonmucinous and 13 mucinous) for hmlh1, hmsh2, and hmsh6 proteins. RESULTS All the tumors showed normal expression of hmlh1, hmsh2, and hmsh6. CONCLUSIONS These findings suggest that defective DNA MMR due to inactivation of hMLH1, hMSH2, or hMSH6 does not play a significant role in the pathogenesis of bronchioloalveolar carcinomas. Cancer 2001;92:2898–901. © 2001 American Cancer Society. Bronchioloalveolar carcinomas of the lung do not show a loss of expression of hmlh1, hmsh2, or hmsh6 by immunohistochemistry. Therefore, DNA mismatch repair resulting from inactivation of hMLH1, hMSH2, or hMSH6 does not likely play a significant role in the pathobiology of this type of lung carcinoma.