title: Correlation between EGFR gene mutation, cytologic tumor markers, 18F-FDG uptake in non-small cell lung cancer.
abstract: BACKGROUND
  EGFR mutation-induced cell proliferation causes changes in tumor biology and tumor metabolism, which may reflect tumor marker concentration and 18F-FDG uptake on PET/CT. Direct aspirates of primary lung tumors contain different concentrations of tumor markers than serum tumor markers, and may correlate better with EGFR mutation than serum tumor markers. The purpose of this study is to investigate an association between cytologic tumor markers and FDG uptake with EGFR mutation status in non-small cell lung cancer (NSCLC).
  
  
  METHODS
  We prospectively collected tumor aspirates of 61 patients who underwent EGFR mutation analysis. Serum and cytologic CYFRA 21-1, CEA, and SCCA levels were measured and correlated with EGFR gene mutations. FDG PET/CT was performed on 58 patients for NSCLC staging, and SUV was correlated with EGFR mutation status.
  
  
  RESULTS
  Thirty (50%) patients had EGFR mutation and 57 patients had adenocarcinoma subtype. Univariate analysis showed that female gender, never smoker, high levels of cytologic CYFRA 21-1 (c-CYFRA) and lower maximum standard uptake value (SUVmax) were correlated with EGFR mutations. ROC generated cut-off values of 20.8 ng/ml for c-CYFRA and SUVmax of 9.6 showed highest sensitivity for EGFR mutation detection. Multivariate analysis revealed that female gender [hazard ratio (HR): 18.15, p = 0.025], higher levels of c-CYFRA (HR: 7.58, and lower SUVmax (HR: 0.08, p = 0.005) were predictive of harboring EGFR mutation.
  
  
  CONCLUSIONS
  The cytologic tumor marker c-CYFRA was positively associated with EGFR mutations in NSCLC. EGFR mutation-positive NSCLCs have relatively lower glycolysis compared with NSCLCs without EGFR mutation.
authors.affiliation: Department of Nuclear Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.|Department of Radiology, Severance Hospital, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Korea.
authors.forename: Arthur
authors.initials: A
authors.lastname: Cho
authors.affiliation: Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea. khuhz@yuhs.ac.
authors.forename: Jin
authors.initials: J
authors.lastname: Hur
authors.affiliation: Yonsei Cancer Center, Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.|Medical Oncology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea.
authors.forename: Yong Wha
authors.initials: YW
authors.lastname: Moon
authors.affiliation: Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Sae Rom
authors.initials: SR
authors.lastname: Hong
authors.affiliation: Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Suh
authors.affiliation: Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Yun Jung
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Dong Jin
authors.initials: DJ
authors.lastname: Im
authors.affiliation: Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Yoo Jin
authors.initials: YJ
authors.lastname: Hong
authors.affiliation: Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Hye-Jeong
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Young Jin
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Hyo Sup
authors.initials: HS
authors.lastname: Shim
authors.affiliation: Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.|Department of Pathology, Dongguk University Ilsan Hospital, Dongguk University College of Medicine, Goyang, Korea.
authors.forename: Jae Seok
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Yonsei Cancer Center, Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.|Medical Oncology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea.
authors.forename: Joo-Hang
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Byoung Wook
authors.initials: BW
authors.lastname: Choi
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D002272:Carcinoembryonic Antigen / Q000097:blood; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation; D003584:Cytological Techniques; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000008:administration & dosage / Q000378:metabolism; D006801:Humans; D053539:Keratin-19 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D049268:Positron-Emission Tomography; D015843:Serpins / Q000097:blood; D014057:Tomography, X-Ray Computed
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D053539:Keratin-19; D015843:Serpins; C102012:antigen CYFRA21.1; C051072:squamous cell carcinoma-related antigen; D019788:Fluorodeoxyglucose F18; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: 18F-FDG PET/CT; Cytologic CYFRA 21-1; Cytologic tumor marker; EGFR mutation