Combination of morphological feature analysis and immunohistochemistry is useful for screening of EML4-ALK-positive lung adenocarcinoma

J Clin Pathol. 2010 Dec;63(12):1066-70. doi: 10.1136/jcp.2010.081166. Epub 2010 Oct 9.

Abstract

Background: A subset of lung cancers harbours the fusion gene echinoderm microtubule-associated protein-like-4-anaplastic lymphoma kinase (EML4-ALK). Recently, immunohistochemistry for ALK has shown sensitivity for the detection of EML4-ALK-positive lung adenocarcinoma almost equal to that of the fluorescence in situ hybridisation (FISH) assay.

Aims: To study the clinicopathological features of EML4-ALK-positive lung adenocarcinoma in a large number of surgically resected samples using immunohistochemistry, in order to establish a useful screening method for EML4-ALK-positive lung adenocarcinoma.

Methods: Immunohistochemistry for ALK was used to screen for EML4-ALK-positive lung adenocarcinomas in 254 cases of surgically resected samples.

Results: EML4-ALK-positive cases were detected in 3.1% of lung adenocarcinomas (8/254). EML4-ALK-positive lung adenocarcinomas showed significant associations with intra- and/or extra-cytoplasmic mucin (p=0.0001), and cribriform pattern with excessive extracytoplasmic mucin (p<0.0001). Signet-ring cell appearance alone lacked significance (p=0.149).

Conclusion: EML4-ALK-positive lung adenocarcinoma has a tendency to express a characteristic morphological pattern. The combined use of morphological feature analysis and immunohistochemistry may be a useful and cost effective screening method for EML4-ALK lung adenocarcinoma.

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology*
  • Adenocarcinoma / surgery
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism*
  • Cell Differentiation
  • Cytoplasm / enzymology
  • Early Detection of Cancer / methods*
  • Female
  • Humans
  • In Situ Hybridization, Fluorescence
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Lung Neoplasms / surgery
  • Male
  • Middle Aged
  • Neoplasm Proteins / metabolism
  • Oncogene Proteins, Fusion / metabolism*

Substances

  • Biomarkers, Tumor
  • EML4-ALK fusion protein, human
  • Neoplasm Proteins
  • Oncogene Proteins, Fusion