title: Class III beta-tubulin is a marker of paclitaxel resistance in carcinomas of unknown primary site.
abstract: OBJECTIVE
  In this study, we determine the prevalence and the prognostic value of the class III beta-tubulin microtubule protein examined immunohistochemically, in tumors of 40 patients with carcinomas of unknown primary site treated with paclitaxel-based chemotherapy.
  
  
  METHODS
  Immunohistochemical intensity of staining and percentage of cells were quantified. Clinical characteristics, response to chemotherapy, progression-free survival, and overall survival were assessed for relationships with the expression of class III beta-tubulin.
  
  
  RESULTS
  The response rate was 17.9% (seven partial responses among 39 valuable patients), while eleven patients had a stable disease (28.2%) and 21 patients progressed on therapy (53.8%). Patients with high class III beta-tubulin expression were more resistant to taxane-based chemotherapy, defined as progression under treatment, while patient characteristics were not found to be correlated with response to chemotherapy. Patients whose tumors expressed high levels of class III beta-tubulin isotype had shorter overall survival, while there was a trend for an association with progression free survival. Multivariate analysis showed that class III beta-tubulin expression was independently correlated with progression free survival and overall survival.
  
  
  CONCLUSIONS
  These findings suggest that a high level of expression of class III beta-tubulin in tumor cells is associated with resistance to paclitaxel and decreased survival in patients with carcinomas of unknown primary receiving paclitaxel-based chemotherapy.
authors.affiliation: Department of Internal Medicine, Hôtel Dieu, 1 Place de l'Hôpital, Hospices Civils de Lyon, 69288, Lyon Cedex 02, France. pascal.seve@chu-lyon.fr
authors.forename: Pascal
authors.initials: P
authors.lastname: Sève
authors.forename: Tony
authors.initials: T
authors.lastname: Reiman
authors.forename: Raymond
authors.initials: R
authors.lastname: Lai
authors.forename: John
authors.initials: J
authors.lastname: Hanson
authors.forename: Cheryl
authors.initials: C
authors.lastname: Santos
authors.forename: Lorelei
authors.initials: L
authors.lastname: Johnson
authors.forename: Laith
authors.initials: L
authors.lastname: Dabbagh
authors.forename: Michael
authors.initials: M
authors.lastname: Sawyer
authors.forename: Charles
authors.initials: C
authors.lastname: Dumontet
authors.forename: John R
authors.initials: JR
authors.lastname: Mackey
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols; D015415:Biomarkers / Q000032:analysis*; D016190:Carboplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009382:Neoplasms, Unknown Primary / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage / Q000627:therapeutic use*; D011379:Prognosis; D016896:Treatment Outcome; D014404:Tubulin / Q000032:analysis*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D015415:Biomarkers; C498585:TUBB3 protein, human; D014404:Tubulin; D016190:Carboplatin; D017239:Paclitaxel