title: Bone sialoprotein is predictive of bone metastases in resectable non-small-cell lung cancer: a retrospective case-control study.
abstract: OBJECTIVE
  Bone metastases (BM) in non-small-cell lung cancer (NSCLC) may be detected at diagnosis or during the course of the disease, and are associated with a worse prognosis. Currently, there are no predictive or diagnostic markers to identify high-risk patients for metastatic bone dissemination.
  
  
  METHODS
  Thirty patients with resected NSCLC who subsequently developed BM were matched for clinicopathologic parameters to 30 control patients with resected NSCLC without any metastases and 26 patients with resected NSCLC and non-BM lesions. Primary tumors were investigated by immunohistochemistry for 10 markers involved in bone resorption or development of metastases. Differences among groups were estimated by chi2 test, whereas the prognostic impact of clinicopathologic parameters and marker expression was evaluated by univariate (Wilcoxon and Mantel-Cox tests) and multivariate (Cox proportional hazards regression model) analyses.
  
  
  RESULTS
  The presence of bone sialoprotein (BSP) was strongly associated with bone dissemination (P < .001) and, independently, with worse outcome (P = .02, Mantel-Cox test), as defined by overall survival. To evaluate BSP protein expression in nonselected NSCLC, a series of 120 consecutive resected lung carcinomas was added to the study, and BSP prevalence reached 40%. No other markers showed a statistically significant difference among the three groups or demonstrated a prognostic impact, in terms of both overall survival and time interval to metastases.
  
  
  CONCLUSIONS
  BSP protein expression in the primary resected NSCLC is strongly associated with BM progression and could be useful in identifying high-risk patients who could benefit from novel modalities of surveillance and preventive treatment.
authors.affiliation: Department of Clinical & Biological Sciences, University of Turin, San Luigi Hospital, Orbassano, Turin, Italy
authors.forename: Mauro
authors.initials: M
authors.lastname: Papotti
authors.forename: Thea
authors.initials: T
authors.lastname: Kalebic
authors.forename: Marco
authors.initials: M
authors.lastname: Volante
authors.forename: Luigi
authors.initials: L
authors.lastname: Chiusa
authors.forename: Elisa
authors.initials: E
authors.lastname: Bacillo
authors.forename: Susanna
authors.initials: S
authors.lastname: Cappia
authors.forename: Paolo
authors.initials: P
authors.lastname: Lausi
authors.forename: Silvia
authors.initials: S
authors.lastname: Novello
authors.forename: Piero
authors.initials: P
authors.lastname: Borasio
authors.forename: Giorgio V
authors.initials: GV
authors.lastname: Scagliotti
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism*; D001859:Bone Neoplasms / Q000556:secondary*; D002289:Carcinoma, Non-Small-Cell Lung / Q000556:secondary*; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D058574:Integrin-Binding Sialoprotein; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D018570:Risk Assessment; D012795:Sialoglycoproteins / Q000032:analysis / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C546871:IBSP protein, human; D058574:Integrin-Binding Sialoprotein; D012795:Sialoglycoproteins