title: Carcinoembryonic antigen-related cell adhesion molecules as surrogate markers for EGFR inhibitor sensitivity in human lung adenocarcinoma.
abstract: BACKGROUND
  Lung adenocarcinoma (LADCA) patients with epidermal growth factor receptor (EGFR) mutations are in general associated with relatively high clinical response rate to EGFR-tyrosine kinase inhibitors (TKIs) but not all responded to TKI. It has therefore become important to identify the additional surrogate markers regarding EGFR-TKI sensitivity.
  
  
  METHODS
  We first examined the effects of EGFR-TKIs, gefitinib and erlotinib, upon cell proliferation of lung adenocarcinoma cell lines. We then evaluated the gene profiles related to EGFR-TKI sensitivity using a microarray analysis. Results of microarray analysis led us to focus on carcinoembryonic antigen-related cell adhesion molecule (CEACAM) family, CEACAM 3, 5, 6, 7, and 19, as potential further surrogate markers of EGFR-TKI sensitivity. We then examined the correlation between the status of CEACAM 3, 5, 6, 7, and 19 immunoreactivity in LADCA and clinicopathological parameters of individual cases.
  
  
  RESULTS
  In the cases with EGFR mutations, the status of all CEACAMs examined was significantly higher than that in EGFR wild-type patients, but there were no significant differences in the status of CEACAMs between TKI responder and nonresponder among 22 patients who received gefitinib therapy. However, among 115 EGFR mutation-negative LADCA patients, both CEACAM6 and CEACAM3 were significantly associated with adverse clinical outcome (CEACAM6) and better clinical outcome (CEACAM3).
  
  
  CONCLUSIONS
  CEACAMs examined in this study could be related to the presence of EGFR mutation in adenocarcinoma cells but not represent the effective surrogate marker of EGFR-TKI in LADCA patients. However, immunohistochemical evaluation of CEACAM3/6 in LADCA patients could provide important information on their clinical outcome.
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Y
authors.initials: Y
authors.lastname: Miki
authors.forename: M
authors.initials: M
authors.lastname: Ebina
authors.forename: K
authors.initials: K
authors.lastname: Abe
authors.forename: K
authors.initials: K
authors.lastname: Mori
authors.forename: S
authors.initials: S
authors.lastname: Narumi
authors.forename: T
authors.initials: T
authors.lastname: Suzuki
authors.forename: I
authors.initials: I
authors.lastname: Sato
authors.forename: M
authors.initials: M
authors.lastname: Maemondo
authors.forename: C
authors.initials: C
authors.lastname: Endo
authors.forename: A
authors.initials: A
authors.lastname: Inoue
authors.forename: H
authors.initials: H
authors.lastname: Kumamoto
authors.forename: T
authors.initials: T
authors.lastname: Kondo
authors.forename: H
authors.initials: H
authors.lastname: Yamada-Okabe
authors.forename: T
authors.initials: T
authors.lastname: Nukiwa
authors.forename: H
authors.initials: H
authors.lastname: Sasano
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D000077192:Adenocarcinoma of Lung; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002272:Carcinoembryonic Antigen / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000069347:Erlotinib Hydrochloride; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology
chemical_list: D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D015815:Cell Adhesion Molecules; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib