Variation in the expression levels of predictive chemotherapy biomarkers in histological subtypes of lung adenocarcinoma: an immunohistochemical study of tissue samples

Int J Clin Exp Pathol. 2015 Sep 1;8(9):10523-33. eCollection 2015.


Background: Lung adenocarcinoma is often composed of a complex and heterogeneous mixture of histological subtypes. Invasive adenocarcinomas are now classified by their predominant pattern, using the comprehensive histological subtyping of the International Association for the Study of Lung Cancer (IASLC), the American Thoracic Society (ATS), and the European Respiratory Society (ERS) classifications. This study aimed to determine whether the expression levels of predictive chemotherapy biomarkers are associated with the histological subtypes proposed by the IASLC/ATS/ERS classification.

Materials and methods: We reviewed data on representative tissue samples from 27 patients who received surgical resection and the expression of excision repair cross complementation group 1 (ERCC1), class III β-tubulin, thymidylate synthase (TS), ribonucleotide reductase M1 (RRM1), and c-Met were examined using immunostaining on tumor tissue slides. We assessed immunohistochemical H-scores, as calculated from the intensity and distribution of intratumor expression, according to the IASLC/ATS/ERS histological subtype.

Results: The expression levels of predictive chemotherapy biomarkers varied according to histological subtype. The H-scores of TS and class III β-tubulin expression levels were higher in solid-type components than they were in lepidic-type components Tumors with solid predominant histology tended to recur earlier than non-solid predominant tumors. However, none of the H-scores in histologically predominant tissues was significantly associated with staging or overall survival.

Conclusions: Immunohistochemical H-scores of the predictive chemotherapy biomarkers were strongly associated with histological subtype. The presence of a solid subtype, which was associated with poor outcomes, might be assessed by measuring these biomarkers in mixed subtype adenocarcinomas.

Keywords: Class III β-tubulin; Thymidylate synthase; c-Met; excision repair cross complementation group 1; immunohistochemistry; ribonucleotide reductase M1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / pathology*
  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / analysis*
  • Drug Resistance, Neoplasm / physiology*
  • Female
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / pathology*
  • Male
  • Middle Aged
  • Retrospective Studies
  • Treatment Outcome


  • Antineoplastic Agents
  • Biomarkers, Tumor