[Frontiers in Bioscience 16, 2961-2969, June 1, 2011]

Detection of EGFR and K-ras mutations for diagnosis of multiple lung adenocarcinomas

Teruo Iwata1, Kenji Sugio1,2, Hidetaka Uramoto1, Sohsuke Yamada3, Takamitsu Onitsuka1, Naohiro Nose1, Kenji Ono1, Mitsuhiro Takenoyama1, Tsunehiro Oyama4, Takeshi Hanagiri1, Kosei Yasumoto1

1 Second Department of Surgery, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan, 2 Department of Thoracic Oncology, National Kyushu Cancer Center, Fukuoka, Japan, 3 Department of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan,4Department of Environmental Health, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan

TABLES OF CONTENTS

1. Abstract
2. Introduction
3. Materials and methods
3.1. Patients
3.2. Histological classification of tissues into Noguchi type A and B
3.3. Detection of EGFR and K-ras mutations
3.4. Statistical analysis
4. Results
4.1. Morphological analysis based on histological classification into Noguchi type A and B
4.2. EGFR and K-ras mutations in the first and the second tumors
4.3. Combined analyses by mutational status of EGFR and K-ras genes and according to Noguchi type A and B
5. Discussion
6. Acknowledgement
7. References

1. ABSTRACT

The incidence of multiple primary lung adenocarcinoma (MPLA) is increasing, and it is important to distinguish MPLA from intrapulmonary metastasis (IPM) in order to determine the therapeutic strategy. However, there is no reliable method to differentiate between the two. The purpose of this study was to distinguish MPLA from IPM based on the gene status of EGFR and K-ras and the morphological Noguchi classification system. Sixty-eight tumors from 34 cases of clinical MPLA were evaluated. Of them, 11 cases (32.4%) were diagnosed as biological MPLA (bMPLA) by EGFR/K-ras mutation analyses, and 12 cases (35.3%) by morphological analysis. In all, 23 of the 34 cases (67.6%) were diagnosed as bMPLA. The remaining 11 cases were diagnosed as biological IPM (bIPM). The 5-year survival rates of bMPLA and bIPM were 90.9% and 63.6%, respectively (p = 0.04). These findings suggest that the combination method including gene mutation and morphological analysis can guide treatment decisions and that there is a need for systemic chemotherapy, and surveillance monitoring.