title: Expression and prognostic implications of apoptosis-related proteins in locally unresectable non-small cell lung cancers.
abstract: BACKGROUND
  Apoptosis related proteins in early staged NSCLC seem to have prognostic value. We studied the value of a combination of eight of those proteins in advanced NSCLC.
  
  
  METHODS
  Bronchoscopically procured tumor biopsies of NSCLC patients were stained immunohistochemically and rated for expression of eight different cellular proteins. Patients were treated with 60 Gy radiotherapy with or without carboplatin as radiosensitizer.
  
  
  RESULTS
  Apoptotic proteins in tumors that showed positive staining were the highest for Bax (99%), Fas (92%), FasL (87%), Rb (87%), p21(WAF1) (73%), and p53 (70%), and the lowest for c-myc (58%) and Bcl-2 (58%). In the Cox regression analysis Bcl-2 positivity (RR = 0.61, 95% CI, 0.37-0.98, p = 0.04) was predictive for overall survival. Only Bcl-2 staining percentage (RR(10) (RR associated with an increase in stained cells of 10%) = 0.93, 95% CI, 0.89-0.99), p53 (RR(10) = 0.94, 95% CI, 0.89-0.99) and FasL (RR(10) = 0.92, 95% CI, 0.86-0.99) were predictive for a longer progression-free survival. No specific constellation of apoptotic proteins was associated with tumor response.
  
  
  CONCLUSIONS
  Bcl-2 expression in tumor tissue of patients with unresectable NSCLC predicts a better overall survival, while Bcl-2, p53, and FasL expressions predict for a longer progression-free survival.
authors.affiliation: Department of Pulmonary Diseases, University Medical Center Groningen, The Netherlands.
authors.forename: Eelco
authors.initials: E
authors.lastname: Fokkema
authors.forename: Wim
authors.initials: W
authors.lastname: Timens
authors.forename: Elisabeth G E
authors.initials: EG
authors.lastname: de Vries
authors.forename: Steven
authors.initials: S
authors.lastname: de Jong
authors.forename: Vaclav
authors.initials: V
authors.lastname: Fidler
authors.forename: Coby
authors.initials: C
authors.lastname: Meijer
authors.forename: Harry J M
authors.initials: HJ
authors.lastname: Groen
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D001706:Biopsy; D001999:Bronchoscopy; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D011013:Pneumonectomy; D011379:Prognosis; D012720:Severity of Illness Index; D015996:Survival Rate
chemical_list: D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor