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. 2016 Apr;142(4):833-43.
doi: 10.1007/s00432-015-2081-4. Epub 2015 Dec 8.

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

Difan Zheng  1   2 , Rui Wang  1   2 , Yang Zhang  1   2 , Yunjian Pan  1   2 , Xinghua Cheng  3 , Chao Cheng  1   2 , Shanbo Zheng  1   2 , Hang Li  1   2 , Ranxia Gong  1   2 , Yuan Li  2   4 , Xuxia Shen  2   4 , Yihua Sun  5   6 , Haiquan Chen  7   8   9   10
Affiliations

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

Difan Zheng et al. J Cancer Res Clin Oncol. 2016 Apr.

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: ALK; Lung adenocarcinoma; Prognosis; Subtypes.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Frequency of gene mutations in 1407 patients with lung adenocarcinoma
Fig. 2
Fig. 2
Relapse-free survival and overall survival in all patients. Kaplan–Meier curve for relapse-free survival and overall survival in 1085 patients with lung adenocarcinoma
Fig. 3
Fig. 3
Frequency of ALK fusion variants in 74 ALK fusion patients
Fig. 4
Fig. 4
Relapse-free survival and overall survival of gender (a, b), smoke status (c, d) and variant subtypes (e, f) in ALK fusion patients
Fig. 5
Fig. 5
Relapse-free survival and overall survival of ALK variant 1 (a, b), variant 2 (c, d) and variant 3 (e, f) in ALK fusion patients
See this image and copyright information in PMC

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