title: ERCC1 expression as a prognostic marker in N2(+) nonsmall-cell lung cancer patients treated with platinum-based neoadjuvant concurrent chemoradiotherapy.
abstract: BACKGROUND
  Excision repair cross-complementation Group 1 (ERCC1) overexpression is associated with resistance to cisplatin-based chemotherapy in patients with nonsmall-cell lung cancer (NSCLC). A preliminary study also suggested that ERCC1 expression is associated with radioresistance in lung cancer cells. The aim of this study was to evaluate the clinical implications of ERCC1 expression in stage IIIA N2-positive NSCLC patients treated with platinum-based neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery.
  
  
  METHODS
  Sixty-eight patients with mediastinoscopy-proven N2-positive NSCLC were enrolled between August 1997 and September 2003. ERCC1 expression was assessed by immunohistochemistry from pretreatment mediastinoscopic biopsy specimens.
  
  
  RESULTS
  ERCC1 expression was positive in 31 of 68 specimens (46%). Among 14 patients who obtained pathologic complete response, 6 were positive for ERCC1 expression and 8 were negative (P = .818). On univariate analysis, with median follow-up of 61.8 months (range, 34.3-108.8 months), progression-free survival was 15.9 months for ERCC1-positive and 29.5 months for ERCC1-negative patients (P = .062), and there was a statistically significant difference in overall survival between ERCC1-negative tumors and ERCC1-positive tumors (89.2 vs 26.0 months, P = .014). On multivariate analysis, ERCC1 negativity (P = .041) and achieving mediastinal nodal clearance (downstage to pathological N0 or N1) after neoadjuvant CCRT followed by surgery (P = .005) were significant independent prognostic factors for the prolongation of survival.
  
  
  CONCLUSIONS
  These results suggest that N2-positive NSCLC patients with ERCC1 negative tumors show a survival benefit from neoadjuvant CCRT with a platinum-containing regimen.
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: In Gyu
authors.initials: IG
authors.lastname: Hwang
authors.forename: Myung Ju
authors.initials: MJ
authors.lastname: Ahn
authors.forename: Byeong Bae
authors.initials: BB
authors.lastname: Park
authors.forename: Yong Chan
authors.initials: YC
authors.lastname: Ahn
authors.forename: Joungho
authors.initials: J
authors.lastname: Han
authors.forename: Seungkoo
authors.initials: S
authors.lastname: Lee
authors.forename: Jhingook
authors.initials: J
authors.lastname: Kim
authors.forename: Young Mog
authors.initials: YM
authors.lastname: Shim
authors.forename: Jin Seok
authors.initials: JS
authors.lastname: Ahn
authors.forename: Keunchil
authors.initials: K
authors.lastname: Park
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000532:radiotherapy / Q000556:secondary; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018572:Disease-Free Survival; D000077143:Docetaxel; D004720:Endonucleases / Q000378:metabolism*; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D004268:DNA-Binding Proteins; D043823:Taxoids; D000077143:Docetaxel; D005047:Etoposide; D016190:Carboplatin; C071447:ERCC1 protein, human; D004720:Endonucleases; D017239:Paclitaxel; D002945:Cisplatin