title: Hypoxia-inducible factor-1α and excision repair cross-complementing 1 in patients with small cell lung cancer who received front-line platinum-based chemotherapy: a retrospective study.
abstract: BACKGROUND
  Hypoxia-inducible factor-1α (HIF-1α), which plays an essential role in the adaptive response of cells to hypoxia, is associated with aggressive tumor behavior. Furthermore, a relationship between excision repair cross-complementing 1 (ERCC1) expression and platinum resistance has been reported in patients with various malignancies. The aim of this study was to investigate the expression of HIF-1α and ERCC1 and to elucidate the clinical significance of their expression in patients with small cell lung cancer (SCLC) treated with front-line platinum-based chemotherapy.
  
  
  METHODS
  SCLC biopsy samples were obtained before front-line platinum-based chemotherapy from 111 patients with SCLC (limited disease, 29; extensive disease [ED], 82) between January 2002 and December 2009 at Gyeongsang National University Hospital. The expression levels of HIF-1α and ERCC1 were assessed by immunohistochemistry.
  
  
  RESULTS
  High expression levels of ERCC1 and HIF-1α were observed in 49 (44.1%) and 71 (64.0%) of 111 patients, respectively. Expression of ERCC1 and HIF-1α was not significantly associated with age, sex, Eastern Cooperative Oncology Group performance status, weight loss, or response to treatment, regardless of stage. In ED-SCLC, low expression in the HIF-1α group showed statistically better survival compared with high expression in the HIF-1α group (p = 0.018). Multivariate analysis revealed that response to front-line platinum-based chemotherapy (p < 0.001), good Eastern Cooperative Oncology Group performance status (0-1) (p = 0.002), and low expression of HIF-1α (p = 0.004) were independent predictors of better overall survival in ED-SCLC.
  
  
  CONCLUSIONS
  Low expression of HIF-1α may be a useful predictor of better overall survival in ED-SCLC patients treated with front-line platinum-based chemotherapy.
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, Gyeongsang National University School of Medicine, Jinju, Republic of Korea.
authors.forename: Gyeong-Won
authors.initials: GW
authors.lastname: Lee
authors.forename: Se Il
authors.initials: SI
authors.lastname: Go
authors.forename: Yu Ji
authors.initials: YJ
authors.lastname: Cho
authors.forename: Yi Yeong
authors.initials: YY
authors.lastname: Jeong
authors.forename: Ho-Cheol
authors.initials: HC
authors.lastname: Kim
authors.forename: Jong
authors.initials: J
authors.lastname: Duk Lee
authors.forename: Young Sil
authors.initials: YS
authors.lastname: Hwang
authors.forename: Gyung Hyuck
authors.initials: GH
authors.lastname: Ko
authors.forename: Jeong Hee
authors.initials: JH
authors.lastname: Lee
authors.forename: Dong Chool
authors.initials: DC
authors.lastname: Kim
authors.forename: Jung Wook
authors.initials: JW
authors.lastname: Yang
authors.forename: Sukjoong
authors.initials: S
authors.lastname: Oh
authors.forename: Jong Sil
authors.initials: JS
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001859:Bone Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D016190:Carboplatin / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004720:Endonucleases / Q000378:metabolism*; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D000077146:Irinotecan; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D005047:Etoposide; D000077146:Irinotecan; D016190:Carboplatin; C071447:ERCC1 protein, human; D004720:Endonucleases; D002945:Cisplatin; D002166:Camptothecin