Epidermal growth factor receptor mutations in multicentric lung adenocarcinomas and atypical adenomatous hyperplasias.
BACKGROUND
The mechanisms of generation and progression of multicentric lung adenocarcinoma (AD), bronchioloalveolar carcinoma (BAC), and atypical adenomatous hyperplasia (AAH) in the peripheral lung is not well known. In this study, we analyzed epidermal growth factor receptor (EGFR) mutations in the cases of multicentric AD, BAC, and AAH to reveal the role of EGFR mutation in their generations and progressions.


METHODS
Ninety-seven AAH, BAC, or AD lesions less than 3 cm in size in 26 patients were surgically resected. Of these, EGFR mutations of the nodules with the highest and the second highest grade of histologic malignancy were examined in each patient by using the peptide nucleic acid-locked nucleic acid polymerase chain reaction (PNA-LNA PCR) clamp method.


RESULTS
EGFR mutations could be examined in 48 nodules in the 26 patients. The EGFR mutations were found more frequently in lesions with higher histologic malignancy, ie, 9 of 10 ADs (90%), 16 of 28 BACs (57%), and one of 10 AAHs (10%). In 22 patients who could be examined of EGFR mutations for the two lesions in each patient, only two patients (9%) had the same mutation patterns between the two lesions, whereas 15 patients (68%) had the different statuses and the remaining five (23%) had no mutations.


CONCLUSIONS
Our data demonstrated that EGFR mutations seem to contribute to the acquisition of malignant potential in the AAH-AD sequence and occur independently in each lesion and in the cases of multicentric AD, BAC, and AAH.
Ikeda
Koei
K
Department of Thoracic Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Nomori
Hiroaki
H
Ohba
Yasuomi
Y
Shibata
Hidekatsu
H
Mori
Takeshi
T
Honda
Yumi
Y
Iyama
Ken-Ichi
K
Kobayashi
Toshiaki
T
D000230:Adenocarcinoma / Q000235:genetics* / Q000601:surgery; D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000235:genetics* / Q000601:surgery; D000368:Aged; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D006801:Humans; D006965:Hyperplasia / Q000235:genetics / Q000601:surgery; D008175:Lung Neoplasms / Q000235:genetics* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction
D066246:ErbB Receptors