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

Background. Defective DNA mismatch repair (MMR) appears to be rare in nonsm all cell carcinomas of the lung. Defective DNA MMR results from genetic or epigenetic alterations that inactivate the DNA MMR genes hMLH1 or hMSH2, an d rarely hMSH6. The loss of normal DNA MMR is thought to promote tumorigene sis by accelerating the accumulation of mutations in oncogenes and tumor su ppressor genes. Inactivation of hMLH1, hMSH2, and hMSH6 is observed as a lo ss of expression of these proteins by immunohistochemistry. Bronchioloalveo lar carcinoma is a subtype of adenocarcinoma with distinctive clinical and pathologic features. Materials and methods. An immunohistochemical study was performed on paraff in embedded sections of 33 bronchioloalveolar carcinomas (20 nonmucinous an d 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 inactivat ion of hMLH-1, hMSH2, or hMSH6 does not play a significant role in the path ogenesis of bronchioloalveolar carcinomas. Cancer 2001;92:2898-901. (C) 200 1 American Cancer Society.