title: Cluster analysis of p-glycoprotein, c-erb-B2 and P53 in relation to tumor histology strongly indicates prognosis in patients with operable non-small cell lung cancer.
abstract: BACKGROUND
  Various biomarkers have prognostic value in non-small cell lung cancer (NSCLC). We aimed to identify the roles of P53, c-erb- B2 and p-glycoprotein (pgp) as prognostic factors, independently or in conjunction with each other, in operable NSCLC.
  
  
  METHODS
  Seventy operable NSCLC cases were retrospectively evaluated for P53, c-erb-B2 and pgp expression patterns by immunohistochemistry. An unsupervised hierarchical cluster analysis of the 3 biomarkers was conducted. Univariate and multivariate survival analyses were made in relation to cluster affiliation.
  
  
  RESULTS
  Cluster analysis yielded two distinct subgroups; group A of high biomarker expressors (n=26, 37%), and group B (n=44, 63%) of low expressors. Cluster affiliation with regard to tumor histology (interaction term) was independently associated with Recurrence- free survival (RFS) and Overall survival (OAS) with a Hazard Ratio (HR) of 5.88, P=0.003, and HR=4.68, P=0.012, respectively. The median OAS times for cluster A and B in the squamous cell carcinoma subgroup were 328 and 596 days, whereas the corresponding figures in the non-squamous cell carcinoma subgroup were non-measurable and 298 days.
  
  
  CONCLUSIONS
  In operable NSCLC there may be different relationships of P53, c-erb-B2 and pgp with patient outcome for different tumor histologies. The prognostic utility of cluster affiliation with regard to these biomarkers, and in relation to tumor histology, deserves further testing.
authors.affiliation: Department of Medical Oncology, Faculty of Medicine, Akdeniz University, Antalya, Turkey. hbozcuk@antnet.net.tr
authors.forename: Hakan
authors.initials: H
authors.lastname: Bozcuk
authors.forename: Aziz
authors.initials: A
authors.lastname: Gumus
authors.forename: Gulay
authors.initials: G
authors.lastname: Ozbilim
authors.forename: Alpay
authors.initials: A
authors.lastname: Sarper
authors.forename: Ilknur
authors.initials: I
authors.lastname: Kucukosmanoglu
authors.forename: Irem H
authors.initials: IH
authors.lastname: Ozbudak
authors.forename: Mehmet
authors.initials: M
authors.lastname: Artac
authors.forename: Mustafa
authors.initials: M
authors.lastname: Ozdogan
authors.forename: Mustafa
authors.initials: M
authors.lastname: Samur
authors.forename: Abit
authors.initials: A
authors.lastname: Kaya
authors.forename: Burhan
authors.initials: B
authors.lastname: Savas
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry / Q000401:mortality / Q000473:pathology* / Q000601:surgery*; D016000:Cluster Analysis; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000737:chemistry / Q000401:mortality / Q000473:pathology* / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D012307:Risk Factors; D012907:Smoking; D016019:Survival Analysis; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53