Sequential Molecular Changes During Multistage Pathogenesis of Small Peripheral Adenocarcinomas of the Lung

Overview

Journal J Thorac Oncol

Publisher Elsevier

Specialties Oncology
Pulmonary Medicine

Date 2008 Apr 2

PMID 18379350

Citations 32

Authors

Junichi Soh

Shinichi Toyooka

Shuji Ichihara

Hiroaki Asano

Naruyuki Kobayashi

Hiroshi Suehisa

Hiroki Otani

Hiromasa Yamamoto

Kouichi Ichimura

Katsuyuki Kiura

Adi F Gazdar

Hiroshi Date

Affiliations

Soon will be listed here.

Abstract

Introduction: We investigated EGFR and KRAS alterations among atypical adenomatous hyperplasia and small lung adenocarcinomas with bronchioloalveolar features to understand their role during multistage pathogenesis.

Methods: Sixty lesions measuring 2 cm or less were studied, including 38 noninvasive lesions (4 atypical adenomatous hyperplasias, 19 Noguchi type A and 15 type B) and 22 invasive lesions (type C) based on the World Health Organization classification and Noguchi's criteria. EGFR and KRAS mutations were examined using PCR-based assays. EGFR copy number was evaluated using fluorescence in situ hybridization.

Results: EGFR and KRAS mutations were found in 26 (43.3%) and 5 (8.3%) lesions, respectively. Increased EGFR copy number status was identified in 10 lesions (16.7%), both mutant and wild type. EGFR or KRAS mutations were present in 39.5% and 7.9% (respectively) of noninvasive lesions and 50% or 9.1% (respectively) of invasive lesions. EGFR copy number was increased in 7.9% and 31.8% of noninvasive and invasive lesions (P = 0.029). Multivariate analysis revealed that increased EGFR copy number was the only significant factor to associate with invasive lesions (P = 0.035).

Conclusions: EGFR and KRAS mutations occur early during the multistage pathogenesis of peripheral lung adenocarcinomas. By contrast, increased EGFR copy number is a late event during tumor development and plays a role in the progression of lung adenocarcinoma independent of the initiating molecular events.

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