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Clinicopathologic characteristics of ALK rearrangements in primary lung adenocarcinoma with identified EGFR and KRAS status

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Abstract

Purpose

EGFR and KRAS genes and ALK arrangements are three genetic drivers of lung adenocarcinoma. The aim of this study was to investigate the clinicopathologic characteristics of the ALK rearrangements in patients with primary lung adenocarcinoma and with identified EGFR or KRAS status.

Methods

Patients with primary lung adenocarcinoma who had enough tissue for study were enrolled. EGFR and KRAS status were identified by DNA sequencing. ALK rearrangements were detected in a tissue microarray by using fluorescent in situ hybridization.

Results

Of 332 patients with primary lung adenocarcinoma, the frequency of the EGFR or the KRAS mutations, and the ALK rearrangements were 44.9 % (149/332), 7.2 % (24/332), and 9.6 % (32/332), respectively. Only one (1/332, 0.3 %) patient had the coexistence of the EGFR mutation (L858R at exon 21) and the ALK rearrangement. Compared with ALK-negative patients, ALK-positive patients were significantly younger (P < 0.001). The incidence of the ALK rearrangements was much higher in EGFR wild-type patients than in those with EGFR mutations (P < 0.001). There was no difference in the gender, smoking, disease stage, or histologic subtypes between the ALK-positive patients and the ALK-negative patients.

Conclusions

The ALK rearrangements are independently associated with younger age and the EGFR wild type. The EGFR mutations and the ALK rearrangements are rarely coexistent. The ALK rearrangements and the KRAS mutations are mutually exclusive.

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Abbreviations

NSCLC:

Non-small cell lung cancer

TKI:

Tyrosine kinase inhibitor

EGFR:

Epidermal growth factor receptor

EML4–ALK:

Echinoderm microtubule-associated protein-like 4 and the anaplastic lymphoma kinase

FDA:

US Food and Drug Administration

FISH:

Fluorescent in situ hybridization

RT-PCR:

Reverse transcriptase polymerase chain reaction

IHC:

Immunohistochemistry

TMA:

Tissue microarray

TNM:

Tumor, node, and metastases

AJCC:

American Joint Committee for Cancer

IASLC/ATS/ERS:

International Association for the Study of Lung Cancer /American Thoracic Society /European Respiratory Society

FFPE:

Formalin-fixed paraffin-embedded

OR:

Odds ratio

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Acknowledgments

This work was supported by the National Science and Technology Major Project of China (2013ZX10003003 and 2012ZX10003002), and Beijing health systems of high-level health and technical personnel training plan (2009-3-51).

Conflict of interest

The authors indicated no potential conflict of interest.

Author information

Authors and Affiliations

  1. Department of Medical Oncology, Beijing Thoracic Tumor and Tuberculosis Research Institute, Beijing Chest Hospital, Capital Medical University, Beijing, 101149, China

    Jinghui Wang, Xi Li, Na Qin, Jingying Nong, Quan Zhang & Shucai Zhang

  2. Department of Pathology, Beijing Thoracic Tumor and Tuberculosis Research Institute, Beijing Chest Hospital, Capital Medical University, Beijing, 101149, China

    Yujie Dong, Yiran Cai, Lijuan Zhou, Dan Su, Jing Mu & Haiqing Zhang

  3. Department of Pathology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, China

    Shafei Wu & Xuan Zeng

  4. Department of Radiotherapy, Beijing Thoracic Tumor and Tuberculosis Research Institute, Beijing Chest Hospital, Capital Medical University, Beijing, 101149, China

    Guimei Liu

  5. Department of Beijing Key Laboratory of Drug Resistance Tuberculosis Research, Beijing Thoracic Tumor and Tuberculosis Research Institute, Beijing Chest Hospital, Capital Medical University, Beijing, 101149, China

    Hongyan Jia & Zongde Zhang

Authors
  1. Jinghui Wang
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  2. Yujie Dong
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  3. Yiran Cai
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  4. Lijuan Zhou
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  7. Dan Su
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  8. Xi Li
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  9. Na Qin
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  10. Jingying Nong
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  12. Quan Zhang
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  13. Jing Mu
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  14. Xuan Zeng
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  15. Haiqing Zhang
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  16. Shucai Zhang
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Corresponding authors

Correspondence to Shucai Zhang or Zongde Zhang.

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Wang, J., Dong, Y., Cai, Y. et al. Clinicopathologic characteristics of ALK rearrangements in primary lung adenocarcinoma with identified EGFR and KRAS status. J Cancer Res Clin Oncol 140, 453–460 (2014). https://doi.org/10.1007/s00432-014-1584-8

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  • DOI: https://doi.org/10.1007/s00432-014-1584-8

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