Immunohistochemical Profile of Neurotrophins and MIB-1 in Jugulotympanic Paragangliomas: Prognostic Value and Review of the Literature

Abstract

Jugulo-tympanic paragangliomas are the most common primary neoplasm of the middle ear, but little is still known about the histological features differentiating the benign and malignant forms. We investigated, with an immunohistochemical procedure, the expression of neurotrophins with their receptors, in fifteen samples of paragangliomas, and MIB-1 in order to consider them as prognostic factors of malignancy. We observed a general positivity for NGF - TrKA - NT4 - TrKC in the cytoplasm, and a strong expression for BDNF in the extracellular space. MIB-1 was moderate in the nucleus of neoplastic cells, weak in the cytoplasm and totally absent in the extracellular space. The comparison between the clinical recurrences and the rate of cytoplasmatic neurotrophins showed strong immunoreactivity in recurrent patients. It should be emphasized that 2 of the 3 recurrences had a wider distribution of the neutrophins, leading to hypothesize the involvement of these substances in the cell proliferation of glomus tumors. Malignant forms of these rare glomus tumors cannot be clearly identified using MIB-1 as a prognostic marker, although we can affirm that neurotrophins and their receptors can be considered as a panel of potential diagnostic markers to monitor the development of such malignancies. Although the small number of patients does not allow definitive conclusions to be made, our findings showed a possible trend towards significance which requires a more powerful study to evaluate this further.