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Open Access Research article

Epidermal growth factor receptor mutations and anaplastic lymphoma kinase rearrangements in lung cancer with nodular ground-glass opacity

Sung-Jun Ko1, Yeon Joo Lee12, Jong Sun Park12, Young-Jae Cho12, Ho Il Yoon12, Jin-Haeng Chung3, Tae Jung Kim4, Kyung Won Lee4, Kwhanmien Kim5, Sanghoon Jheon5, Hyojin Kim6, Jae Ho Lee12 and Choon-Taek Lee12*

Author Affiliations

1 Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea

2 Department of Internal Medicine, Seoul National University Bundang Hospital, 173-82 Gumi-Ro, Bundang-Gu, Seongnam 464-707, Korea

3 Department Pathology, Seoul National University College of Medicine, Seongnam, Korea

4 Department of Radiology, Seoul National University Bundang Hospital, Seongnam, Korea

5 Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seongnam, Korea

6 Department of Pathology, Seoul National University Hospital, Seoul, Korea

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BMC Cancer 2014, 14:312  doi:10.1186/1471-2407-14-312

Published: 3 May 2014

Abstract

Background

Nodular ground-glass opacities (nGGO) are a specific type of lung adenocarcinoma. ALK rearrangements and driver mutations such as EGFR and K-ras are frequently found in all types of lung adenocarcinoma. EGFR mutations play a role in the early carcinogenesis of nGGOs, but the role of ALK rearrangement remains unknown.

Methods

We studied 217 nGGOs resected from 215 lung cancer patients. Pathology, tumor size, tumor disappearance rate, and the EGFR and ALK markers were analyzed.

Results

All but one of the resected nGGOs were adenocarcinomas. ALK rearrangements and EGFR mutations were found in 6 (2.8%) and 119 (54.8%) cases. The frequency of ALK rearrangement in nGGO was significantly lower than previously reported in adenocarcinoma. Advanced disease stage (pā€‰=ā€‰0.018) and larger tumor size (pā€‰=ā€‰0.037) were more frequent in the ALK rearrangement-positive group than in ALK rearrangement-negative patients. nGGOs with ALK rearrangements were associated with significantly higher pathologic stage and larger maximal and solid diameter in comparison to EGFR-mutated lesions.

Conclusion

ALK rearrangement is rare in lung cancer with nGGOs, but is associated with advanced stage and larger tumor size, suggesting its association with aggressive progression of lung adenocarcinoma. ALK rearrangement may not be important in early pathogenesis of nGGO.

Keywords:
Lung cancer; Adenocarcinoma; nGGO; ALK; EGFR