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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / chemistry
  • Adenocarcinoma / epidemiology
  • Adenocarcinoma / etiology
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology*
  • Adenocarcinoma of Lung
  • Adult
  • Aged
  • Aged, 80 and over
  • Anaplastic Lymphoma Kinase
  • Asian People / genetics
  • Asian People / statistics & numerical data*
  • China / epidemiology
  • Disease-Free Survival
  • ErbB Receptors / analysis
  • ErbB Receptors / genetics
  • Female
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Lung Neoplasms / chemistry
  • Lung Neoplasms / epidemiology
  • Lung Neoplasms / etiology
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology*
  • Male
  • Middle Aged
  • Mutation*
  • Neoplasm Recurrence, Local / epidemiology
  • Neoplasm Recurrence, Local / etiology
  • Neoplasm Staging
  • Oncogene Proteins, Fusion / analysis*
  • Oncogene Proteins, Fusion / genetics*
  • Predictive Value of Tests
  • Prevalence
  • Prognosis
  • Protein-Tyrosine Kinases / analysis
  • Protein-Tyrosine Kinases / genetics
  • Proto-Oncogene Proteins / analysis
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins B-raf / analysis
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins c-ret / analysis
  • Proto-Oncogene Proteins c-ret / genetics
  • Proto-Oncogene Proteins p21(ras) / analysis
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Real-Time Polymerase Chain Reaction
  • Receptor Protein-Tyrosine Kinases / analysis
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Receptor, ErbB-2 / analysis
  • Receptor, ErbB-2 / genetics
  • Retrospective Studies
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sex Factors
  • Smoking / adverse effects
  • Survival Analysis

Substances

  • EML4-ALK fusion protein, human
  • KRAS protein, human
  • Oncogene Proteins, Fusion
  • Proto-Oncogene Proteins
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • EGFR protein, human
  • ERBB2 protein, human
  • ErbB Receptors
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-ret
  • RET protein, human
  • ROS1 protein, human
  • Receptor Protein-Tyrosine Kinases
  • Receptor, ErbB-2
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • Proto-Oncogene Proteins p21(ras)