Expression patterns of Trk-A, Trk-B, GRP78, and p75NRT in olfactory neuroblastoma

Hum Pathol. 2009 Sep;40(9):1330-5. doi: 10.1016/j.humpath.2009.02.001. Epub 2009 Apr 22.

Abstract

Olfactory neuroblastoma is an uncommon neuroectodermal tumor of the sinonasal tract. It represents 2% to 3% of sinonasal neoplasms. Most olfactory neuroblastoma behave locally aggressive with 30% recurrence rates. A subset metastasizes to lymph nodes and/or distant sites. Grading of olfactory neuroblastoma involves a combination of factors with low-grade tumors having better survival than high-grade tumors. The grade does not always predict prognosis, however, as metastases can be seen in all grades of olfactory neuroblastoma. Trk-A, Trk-B, and p75NRT are neurotrophin receptors associated with numerous solid malignancies, particularly pediatric neuroblastoma. GRP78 is an endoplasmic reticulum protein, associated with differentiation of neuroblastic cells. Trk-A, p75NRT, and GRP78 overexpression are favorable prognostic factors in pediatric neuroblastoma, whereas Trk-B is associated with a poorer prognosis in these tumors. Olfactory neuroblastoma is clinically distinct from pediatric neuroblastoma but shares some histological features. Trk-A and p75NRT have been demonstrated in olfactory neuroblastoma previously. Trk-B and GRP78 have not been investigated in olfactory neuroblastoma. None of these markers have been correlated with grade or outcome in olfactory neuroblastoma. To investigate the role of Trk-A, Trk-B, p75NRT, and GRP78, a series of 20 olfactory neuroblastomas was stained with these antibodies. Trk-A and Trk-B stained most cases of olfactory neuroblastoma (90% and 85%). GRP78 stained most cases (90%), although weakly. P75NRT demonstrated focal membranous staining in a sustentacular pattern (60%). None of these markers correlated with Hyams grade. None of these markers definitively correlated with patient outcome. Neurotrophin receptors do not appear to have a prognostic role; however, Trk's may play an oncogenic role in olfactory neuroblastoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / genetics
  • Child
  • Endoplasmic Reticulum Chaperone BiP
  • Esthesioneuroblastoma, Olfactory / genetics*
  • Esthesioneuroblastoma, Olfactory / pathology
  • Esthesioneuroblastoma, Olfactory / radiotherapy
  • Esthesioneuroblastoma, Olfactory / surgery
  • Female
  • Follow-Up Studies
  • Gene Expression
  • Gene Expression Regulation, Neoplastic
  • Heat-Shock Proteins / genetics*
  • Humans
  • Male
  • Middle Aged
  • Receptor, Nerve Growth Factor / genetics*
  • Receptor, trkA / genetics*
  • Receptor, trkB / genetics*
  • Survival Analysis
  • Time Factors
  • Treatment Outcome
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Endoplasmic Reticulum Chaperone BiP
  • HSPA5 protein, human
  • Heat-Shock Proteins
  • Receptor, Nerve Growth Factor
  • Receptor, trkA
  • Receptor, trkB