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Published on: February 28, 2019
Expression patterns of Trk-A, Trk-B, GRP78, and p75NRT in olfactory neuroblastoma
Ilan Weinreb1, David Goldstein, Jonathan Irish
1Department of Pathology, University Health Network, Toronto, Ontario, Canada. weinrebi@yahoo.ca
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.
Insights
Neurotrophin receptors Trk-A, Trk-B, and p75NRT, along with GRP78, were investigated in olfactory neuroblastoma. These markers did not correlate with tumor grade or patient outcomes, suggesting a limited prognostic role.
Area of Science:
- Oncology
- Molecular Pathology
- Cancer Research
Background:
- Olfactory neuroblastoma is a rare sinonasal tumor with aggressive local behavior and potential for metastasis.
- Neurotrophin receptors (Trk-A, Trk-B, p75NRT) and GRP78 are implicated in pediatric neuroblastoma prognosis but unstudied in olfactory neuroblastoma.
- Previous studies show Trk-A and p75NRT in olfactory neuroblastoma, but Trk-B and GRP78 roles remain unclear.
Purpose of the Study:
- To investigate the expression and potential prognostic significance of Trk-A, Trk-B, p75NRT, and GRP78 in olfactory neuroblastoma.
- To correlate the expression of these markers with tumor grade (Hyams grade) and patient outcomes.
- To explore the potential oncogenic role of Trk receptors in olfactory neuroblastoma.
Main Methods:
- Immunohistochemical staining for Trk-A, Trk-B, p75NRT, and GRP78 was performed on a series of 20 olfactory neuroblastoma tissue samples.
- Expression levels and patterns of the markers were analyzed.
- Correlations between marker expression, Hyams grade, and patient outcomes were assessed.
Main Results:
- Trk-A (90%), Trk-B (85%), and GRP78 (90%, weak) were expressed in most olfactory neuroblastoma cases.
- P75NRT showed focal sustentacular staining in 60% of cases.
- No significant correlation was found between the expression of Trk-A, Trk-B, p75NRT, or GRP78 and Hyams grade or patient prognosis.
Conclusions:
- Neurotrophin receptors Trk-A, Trk-B, p75NRT, and GRP78 do not appear to have a prognostic role in olfactory neuroblastoma.
- Despite lacking prognostic value, Trk receptors might be involved in the oncogenesis of olfactory neuroblastoma.
- Further research is needed to elucidate the specific role of Trk signaling pathways in olfactory neuroblastoma development.
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