Japanese Journal of Clinical Oncology Advance Access originally published online on December 18, 2007
Japanese Journal of Clinical Oncology 2007 37(12):907-912; doi:10.1093/jjco/hym139
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© 2007 Foundation for Promotion of Cancer Research
Molecular Markers and Changes of Computed Tomography Appearance in Lung Adenocarcinoma with Ground-glass Opacity
1 Cancer Genomics Project, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
2 Proteome Bioinformatics Project, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
3 Pathology Division, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045
4 Thoracic Surgery Division, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
5 Clinical Laboratory Division, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
6 Diagnostic Radiology Division, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
For reprints and all correspondence: Tatsuhiro Shibata, Cancer Genomics Project, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. E-mail: tashibat{at}ncc.go.jp
Received March 31, 2007; accepted July 5, 2007
Background: High-resolution computed tomography (HRCT) of lung adenocarcinoma at early stage shows pure ground-glass opacity (GGO) and most cases of pure GGO remain stable during follow-up. There is no consensus on the strategy for follow-up. Identification of the molecular mechanisms that are associated with the natural history of lung adenocarcinoma should provide useful information.
Methods: Twenty-three lung adenocarcinomas that were followed-up for more than 6 months pre-operatively by HRCT were included in this study. Patterns of radiological changes during the follow-up period were classified into three groups; type 1, pure GGO without consolidation; type 2, appearance or increase in consolidation within pure GGO; type 3, consolidation without pure GGO. Mutational analysis of the epidermal growth factor receptor (EGFR) and K-ras genes and immunohistochemical staining of p53 protein were performed.
Results: EGFR mutations were found in 17 cases (74%), and there was no K-ras mutation. Positive staining of p53 was found in 8 cases (35%). As for radiological findings during the follow-up period, the frequencies of EGFR mutations and positive p53 staining were 67 and 0% in type 1 (n = 9), 89 and 44% in type 2 (n = 9) and 60 and 80% in type 3 (n = 5).
Conclusions: EGFR mutations were frequently found in lung adenocarcinoma with GGO on HRCT in this study. Inactivation of p53 may be associated with the appearance of central consolidation within pure GGO on HRCT which reflects invasive features and may be useful as a molecular marker during the follow-up of pure GGO.
Key Words: lung neoplasms • tomography • spiral computed receptor • epidermal growth factor • tumor suppressor protein p53 • adenocarcinoma • bronchioloalveolar
7 Present address: Department of Thoracic Surgery, The University of Tokyo Hospital, Tokyo, Japan