title: Interferon-α/β receptor as a prognostic marker in osteosarcoma.
abstract: BACKGROUND
  A large-scale randomized trial of adjuvant interferon-α therapy for patients with osteosarcoma has been initiated as a joint protocol by the European and American Osteosarcoma Study Group. Because the expression of functional interferon-α/β receptor is necessary for interferon-α agents to interact with osteosarcoma cells, we examined the expression of interferon-α/β receptor in a series of osteosarcoma specimens.
  
  
  METHODS
  Forty patients with high-grade resectable osteosarcoma, from whom surgical specimens had been obtained at the time of biopsy, were included in this retrospective study. Biopsy specimens were immunohistochemically stained with anti-interferon-α/β receptor antibodies. Survival was estimated with the Kaplan-Meier method. The Cox proportional hazards model was used for multivariate analysis to determine the independent prognostic factors. Furthermore, we used Holm and Benjamini-Hochberg procedures to adjust for multiple comparisons in setting the level of significance. The median follow-up period was five years and two months (range, four to 195 months).
  
  
  RESULTS
  The expression of interferon-α/β receptor was positive in eighteen (45%) of the forty patients with high-grade osteosarcoma. American Joint Committee on Cancer surgical stage IIA, a good histologic response to chemotherapy, and expression of interferon-α/β receptor correlated significantly with better disease-free survival (p < 0.05). Multivariate analysis showed that interferon-α/β receptor expression alone retained its power to predict an improved prognosis (p = 0.042). There were no significant variables after corrections for multiple comparisons.
  
  
  CONCLUSIONS
  Interferon-α/β receptor may be a useful marker for assessing tumor prognosis in patients with osteosarcoma and may play an important role in tumor progression. These findings are encouraging and support the ongoing clinical trials of adjuvant interferon-α therapy by the multinational Osteosarcoma Study Group. Our pilot study was based on a small sample size, and larger trials are needed to confirm this finding.
  
  
  METHODS
  Prognostic Level II. See Instructions to Authors for a complete description of levels of evidence.
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Japan. kubot@hiroshima-u.ac.jp
authors.forename: Tadahiko
authors.initials: T
authors.lastname: Kubo
authors.forename: Shoji
authors.initials: S
authors.lastname: Shimose
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Matsuo
authors.forename: Jun
authors.initials: J
authors.lastname: Fujimori
authors.forename: Koji
authors.initials: K
authors.lastname: Arihiro
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Ochi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D015415:Biomarkers; D001859:Bone Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002648:Child; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007370:Interferon Type I / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D012516:Osteosarcoma / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D011379:Prognosis; D053633:Receptor, Interferon alpha-beta / Q000032:analysis*; D011994:Recombinant Proteins; D015996:Survival Rate; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D007370:Interferon Type I; D011994:Recombinant Proteins; D053633:Receptor, Interferon alpha-beta