title: Variation in the expression levels of predictive chemotherapy biomarkers in histological subtypes of lung adenocarcinoma: an immunohistochemical study of tissue samples.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Respiratory Medicine, Juntendo University Faculty of Medicine & Graduate School of Medicine 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan ; Research Institute for Diseases of Old Ages, Juntendo University Graduate School of Medicine 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Fujimoto
authors.affiliation: Department of Respiratory Medicine, Juntendo University Faculty of Medicine & Graduate School of Medicine 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan ; Research Institute for Diseases of Old Ages, Juntendo University Graduate School of Medicine 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan.
authors.forename: Shinsaku
authors.initials: S
authors.lastname: Togo
authors.affiliation: Department of Respiratory Medicine, Juntendo University Faculty of Medicine & Graduate School of Medicine 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan ; Research Institute for Diseases of Old Ages, Juntendo University Graduate School of Medicine 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan.
authors.forename: Miniwan
authors.initials: M
authors.lastname: Tulafu
authors.affiliation: Department of Respiratory Medicine, Juntendo University Faculty of Medicine & Graduate School of Medicine 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan ; Research Institute for Diseases of Old Ages, Juntendo University Graduate School of Medicine 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan.
authors.forename: Kazue
authors.initials: K
authors.lastname: Shimizu
authors.affiliation: Department of Pathology, Juntendo University School of Medicine 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan.
authors.forename: Takuo
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: Department of Pathology, Labor Health and Welfare Organization Kanto Rosai Hospital 1-1 Kizukisumiyoshi-cho, Nakahara-Ku, Kawasaki, Kanagawa Prefecture 211-8510, Japan.
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Uekusa
authors.affiliation: Department of Respiratory Medicine, Juntendo University Faculty of Medicine & Graduate School of Medicine 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan ; Research Institute for Diseases of Old Ages, Juntendo University Graduate School of Medicine 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan.
authors.forename: Yuichirou
authors.initials: Y
authors.lastname: Honma
authors.affiliation: Department of Respiratory Medicine, Juntendo University Faculty of Medicine & Graduate School of Medicine 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan ; Research Institute for Diseases of Old Ages, Juntendo University Graduate School of Medicine 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Namba
authors.affiliation: Department of General Thoracic Surgery, Juntendo University School of Medicine 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Takamochi
authors.affiliation: Department of General Thoracic Surgery, Juntendo University School of Medicine 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan.
authors.forename: Shiaki
authors.initials: S
authors.lastname: Oh
authors.affiliation: Department of General Thoracic Surgery, Juntendo University School of Medicine 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Department of Respiratory Medicine, Juntendo University Faculty of Medicine & Graduate School of Medicine 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan ; Research Institute for Diseases of Old Ages, Juntendo University Graduate School of Medicine 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Takahashi
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology*; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis*; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor
keywords: Class III β-tubulin; Thymidylate synthase; c-Met; excision repair cross complementation group 1; immunohistochemistry; ribonucleotide reductase M1