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 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.


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.
Aubry
M C
MC
Department of Laboratory Medicine and Pathology, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA. aubry.mariechristine@mayo.edu
Halling
K C
KC
Myers
J L
JL
Tazelaar
H D
HD
Yang
P
P
Thibodeau
S N
SN
D048868:Adaptor Proteins, Signal Transducing; D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D020137:Base Pair Mismatch; D002352:Carrier Proteins; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000378:metabolism*; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein