Clonality status of multifocal lung adenocarcinomas based on the mutation patterns of EGFR and K-ras.
OBJECTIVE
The purpose of this study is to clarify the clonality status of multifocal lung adenocarcinomas based on the mutation patterns of epidermal growth factor receptor (EGFR) and K-ras.


METHODS
We analyzed 82 multifocal lung adenocarcinomas from 36 patients who underwent surgical resection. Genomic DNA was extracted from formalin-fixed, paraffin-embedded tissue and analyzed for EGFR and K-ras mutations. We determined the clonality status of multifocal lung adenocarcinomas based on the mutation patterns of EGFR and K-ras. The actuarial survival time was estimated and the prognostic factors were evaluated for 31 patients with synchronous multifocal lung adenocarcinomas.


RESULTS
EGFR and K-ras mutations were detected in 36 (44%) and 19 (23%) of the 82 tumors, respectively. EGFR mutations had occurred randomly in 20 (91%) of the 22 patients with at least one EGFR mutated tumor. K-ras mutations had occurred randomly in 14 (93%) of the 15 patients with at least one K-ras mutated tumor. Combining the results for the EGFR and K-ras mutation patterns, the clonality status of multifocal lung adenocarcinomas could be determined in 30 (83%) of the 36 patients. No statistically significant difference in the actuarial survival of the patient subgroups stratified according to the clonality status, which was based on the presence of EGFR and K-ras mutations, was observed.


CONCLUSIONS
Both EGFR and K-ras mutations frequently occur randomly in multifocal lung adenocarcinomas. Combined mutation pattern analyses of EGFR and K-ras may be useful for making decisions regarding treatment strategies for patients with multifocal lung adenocarcinomas.
Department of General Thoracic Surgery, Juntendo University School of Medicine, 1-3, Hongo 3-chome, Bunkyo-ku, Tokyo 113-8431, Japan.
Kazuya
K
Takamochi
Shiaki
S
Oh
Joe
J
Matsuoka
Kenji
K
Suzuki
D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D011905:Genes, ras; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009378:Neoplasms, Multiple Primary / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000601:surgery; D011237:Predictive Value of Tests; D015996:Survival Rate
C512478:EGFR protein, human; D066246:ErbB Receptors