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Prevalence and clinicopathological characteristics of ALK fusion subtypes in lung adenocarcinomas from Chinese populations

  • Difan Zheng
  • Rui Wang
  • Yang Zhang
  • Yunjian Pan
  • Xinghua Cheng
  • Chao Cheng
  • Shanbo Zheng
  • Hang Li
  • Ranxia Gong
  • Yuan Li
  • Xuxia Shen
  • Yihua SunEmail author
  • Haiquan ChenEmail author
Original Article – Clinical Oncology

Abstract

Purpose

We performed this retrospective study to have a comprehensive investigation of the clinicopathological characteristics of ALK fusion-positive lung adenocarcinoma in Chinese populations.

Methods

We screened 1407 patients with primary lung adenocarcinoma from October 2007 to May 2013. Quantitative real-time PCR (qRT-PCR), reverse transcriptase PCR (RT-PCR), and fluorescence in situ hybridization were performed to detect ALK fusion genes, with validation of positive results using immunohistochemistry. Clinicopathological characteristics were collected to assess prognosis in ALK fusion-positive patients.

Results

Of 1407 patients with lung adenocarcinoma, there were 74 (5.3 %) ALK fusion-positive patients. Patients harboring ALK fusion were significantly younger (56.0 years vs. 59.8 years p = 0.002) and were more likely to have advanced stages (stage III or stage IV) (OR 1.761; 95 % CI 1.10–2.82, p = 0.017). Lepidic predominant adenocarcinoma was rarely found in ALK fusion patients (2.7 vs. 13.5 % p = 0.025), while IMA (invasive mucinous adenocarcinoma) predominant adenocarcinoma was more frequently found (21.6 vs. 5.0 % p < 0.001). ALK fusion was neither a risk factor nor protective factor in relapse-free survival and overall survival. Male, current smoker, and EML4-ALK variant 3 indicated poor prognosis among ALK fusion-positive lung adenocarcinomas.

Conclusions

ALK fusion was detected in 5.3 % (74/1407) of the Chinese patients with lung adenocarcinoma. ALK fusion defines a molecular subset of lung adenocarcinoma with unique clinicopathological characteristics. Different ALK fusion variants determine distinct prognoses.

Keywords

Lung adenocarcinoma ALK Subtypes Prognosis 

Notes

Acknowledgments

This work was funded by the National Natural Science Foundation of China (81330056, 81401886, 81401891, 81422029, 81472173 and 81372525), the Key Project of Science and Technology Commission of Shanghai Municipality (JGGG1302) and Shen-Kang Center Project (SKMB1201).

Author contributions

Dr Haiquan Chen is the guarantor of the manuscript. Dr Difan Zheng contributed to conception and study design, acquisition and analysis of data, and writing and revision of the manuscript. Dr Rui. Wang contributed to conception and study design, acquisition and analysis of data, and writing and revision of the manuscript. Dr Yang Zhang contributed to conception and study design, acquisition and analysis of data, and writing and revision of the manuscript. Dr Yunjian Pan contributed to acquisition of data and writing and revision of the manuscript. Dr Xinghua Cheng contributed to acquisition of data and writing and revision of the manuscript. Dr Chao Cheng contributed to analysis of data and revision of the manuscript. Dr Shanbo Zheng contributed to acquisition of data and revision of the manuscript. Dr Hang Li. Wang contributed to acquisition of data and revision of the manuscript. Dr Ranxia Gong contributed to acquisition of data and revision of the manuscript. Dr Yuan Li contributed to acquisition of data and revision of the manuscript. Dr Xuxia Shen contributed to analysis of data and revision of the manuscript. Dr Yihua Sun contributed to conception and study design, review and revision of the manuscript. Dr Haiquan Chen contributed to conception and study design, analysis of data, and review and revision of the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Written informed consent was obtained from each patient to allow their biological samples to be genetically analyzed.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Difan Zheng
    • 1
    • 2
  • Rui Wang
    • 1
    • 2
  • Yang Zhang
    • 1
    • 2
  • Yunjian Pan
    • 1
    • 2
  • Xinghua Cheng
    • 4
  • Chao Cheng
    • 1
    • 2
  • Shanbo Zheng
    • 1
    • 2
  • Hang Li
    • 1
    • 2
  • Ranxia Gong
    • 1
    • 2
  • Yuan Li
    • 2
    • 3
  • Xuxia Shen
    • 2
    • 3
  • Yihua Sun
    • 1
    • 2
    Email author
  • Haiquan Chen
    • 1
    • 2
    • 4
    • 5
    Email author
  1. 1.Department of Thoracic SurgeryFudan University Shanghai Cancer CenterShanghaiChina
  2. 2.Department of Oncology, Shanghai Medical CollegeFudan UniversityShanghaiChina
  3. 3.Department of PathologyFudan University Shanghai Cancer CenterShanghaiChina
  4. 4.Shanghai Chest HospitalShanghai Jiao Tong UniversityShanghaiChina
  5. 5.Institutes of Biomedical SciencesFudan UniversityShanghaiChina

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