title: βV-tubulin expression is associated with outcome following taxane-based chemotherapy in non-small cell lung cancer.
abstract: BACKGROUND
  Tubulin-binding agents (TBAs) are effective in non-small cell lung cancer (NSCLC) treatment. Both βIII- and βV-tubulins are expressed by cancer cells and may lead to resistance against TBAs.
  
  
  METHODS
  Pre-treatment samples from 65 locally advanced or oligometastatic NSCLC patients, who underwent uniform induction chemotherapy with paclitaxel and platinum followed by radiochemotherapy with vinorelbine and platinum were retrospectively analysed by immunohistochemistry. Protein expression of βIII- and βV-tubulin was morphometrically quantified.
  
  
  RESULTS
  Median pre-treatment H-score for βIII-tubulin was 110 (range: 0-290), and 160 for βV-tubulin (range: 0-290). Low βIII-tubulin expression was associated with improved overall survival (OS) (P=0.0127, hazard ratio (HR): 0.328). An association between high βV-tubulin expression and prolonged progression-free survival (PFS, median 19.2 vs 9.4 months in high vs low expressors; P=0.0315, HR: 1.899) was found. Further, high βV-tubulin expression was associated with objective response (median H-score 172.5 for CR+PR vs 120 for SD+PD patients, P=0.0104) or disease control following induction chemotherapy (170 for CR+PR+SD vs 100 for PD patients, P=0.0081), but not radiochemotherapy.
  
  
  CONCLUSIONS
  Expression of βV-tubulin was associated with treatment response and PFS following paclitaxel-based chemotherapy of locally advanced and oligometastatic NSCLC patients. Prolonged OS was associated with low levels of βIII-tubulin. Prospective evaluation of βIII/βV-tubulin expression in NSCLC is warranted.
authors: Department of Medical Oncology, West German Cancer Centre, University Hospital Essen, University Duisburg-Essen, Hufelandstrasse 55, Essen 45147, Germany. daniel.christoph@uk-essen.de
authors: D C
authors: DC
authors: Christoph
authors: S
authors: S
authors: Kasper
authors: T C
authors: TC
authors: Gauler
authors: C
authors: C
authors: Loesch
authors: M
authors: M
authors: Engelhard
authors: D
authors: D
authors: Theegarten
authors: C
authors: C
authors: Poettgen
authors: R
authors: R
authors: Hepp
authors: A
authors: A
authors: Peglow
authors: H
authors: H
authors: Loewendick
authors: S
authors: S
authors: Welter
authors: G
authors: G
authors: Stamatis
authors: F R
authors: FR
authors: Hirsch
authors: M
authors: M
authors: Schuler
authors: W E E
authors: WE
authors: Eberhardt
authors: J
authors: J
authors: Wohlschlaeger
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001952:Bridged-Ring Compounds / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D043823:Taxoids / Q000008:administration & dosage; D014162:Transfection; D016896:Treatment Outcome; D014404:Tubulin / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D001952:Bridged-Ring Compounds; D043823:Taxoids; D014404:Tubulin; C507416:tubulin betaV, human; C080625:taxane