title: Evaluation of P-glycoprotein, HER-2/ErbB-2, p53, and Bcl-2 in primary tumor and metachronous lung metastases in patients with high-grade osteosarcoma.
abstract: BACKGROUND
  Investigation of the relation between primary tumor and metastatic disease is necessary for the identification of predictive factors for postrecurrence survival (PRS) in patients with recurrent osteosarcoma.
  
  
  METHODS
  Cellular levels of P-glycoprotein, ErbB-2, p53, and Bcl-2 expression were evaluated in primary tumor biopsy and metachronous pulmonary metastasis specimens from 19 patients with high-grade osteosarcoma. Results were analyzed for differences between primary tumor and pulmonary metastases and for correlations between expression patterns and survival.
  
  
  RESULTS
  Positive staining in lung metastases was noted in 68%, 53%, 32%, and 84% of patients for P-glycoprotein, ErbB-2, p53, and Bcl-2, respectively. These percentages were higher than those observed in primary tumor specimens for all genetic markers evaluated, with a significant difference in the percentage of patients with positive staining for P-glycoprotein (68% vs. 32%; P = 0.05) and a near-significant difference in the percentage of patients with positive staining for Bcl-2 (84% vs. 53%; P = 0.08). Patients with ErbB-2 expression in the primary tumor were more likely to have multiple metastases and shorter recurrence-free intervals compared with patients in whom ErbB-2 expression was not observed, whereas differences in P-glycoprotein, p53, and Bcl-2 expression were not related to differences in metastatic pattern. PRS was influenced by p53 expression levels in pulmonary metastases, with patients who had negative staining for p53 having a significantly better PRS rate relative to patients with positive staining for p53 (3-year PRS rate: p53-negative, 64%; p53-positive, 17%; P = 0.008).
  
  
  CONCLUSIONS
  In the current study of patients with high-grade osteosarcoma, most patients exhibited increased cellular expression of P-glycoprotein, ErbB-2, and Bcl-2 in recurrent pulmonary metastases compared with primary tumor. Further studies aimed at investigating the relation between altered p53 expression in lung metastases and postrecurrence survival are recommended.
authors.affiliation: Chemotherapy Service, Department of Musculoskeletal Oncology, Istituti Ortopedici Rizzoli, Bologna, Italy. stefano.ferrari@ior.it
authors.forename: Stefano
authors.initials: S
authors.lastname: Ferrari
authors.forename: Franco
authors.initials: F
authors.lastname: Bertoni
authors.forename: Licciana
authors.initials: L
authors.lastname: Zanella
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Setola
authors.forename: Patrizia
authors.initials: P
authors.lastname: Bacchini
authors.forename: Marco
authors.initials: M
authors.lastname: Alberghini
authors.forename: Michela
authors.initials: M
authors.lastname: Versari
authors.forename: Gaetano
authors.initials: G
authors.lastname: Bacci
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis; D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000097:blood*; D001859:Bone Neoplasms / Q000401:mortality* / Q000473:pathology* / Q000628:therapy; D002648:Child; D015331:Cohort Studies; D005260:Female; D006023:Glycoproteins / Q000032:analysis; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality* / Q000556:secondary* / Q000628:therapy; D008297:Male; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology / Q000628:therapy; D009367:Neoplasm Staging; D012516:Osteosarcoma / Q000401:mortality* / Q000556:secondary* / Q000628:therapy; D011336:Probability; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D012189:Retrospective Studies; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014408:Biomarkers, Tumor; D006023:Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53