A mosaic pattern of INI1/SMARCB1 protein expression distinguishes Schwannomatosis and NF2-associated peripheral schwannomas from solitary peripheral schwannomas and NF2-associated vestibular schwannomas.

Autor: Caltabiano R; Department of Medical and Surgical Sciences and Advanced Technologies 'G. F. Ingrassia', Section of Anatomic Pathology, University of Catania, Catania, Italy., Magro G; Department of Medical and Surgical Sciences and Advanced Technologies 'G. F. Ingrassia', Section of Anatomic Pathology, University of Catania, Catania, Italy., Polizzi A; National Centre for Rare Diseases, Istituto Superiore di Sanità, Rome, Italy.; Institute of Neurological Sciences, National Research Council, Catania, Italy., Praticò AD; Unit of Rare Diseases of the Nervous System in Childhood, Department of Clinical and Experimental Medicine, Section of Pediatrics and Child Neuropsychiatry, University of Catania, AOU 'Policlinico-Vittorio Emanuele', Via S. Sofia, 78, 95124, Catania, Italy.; Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy., Ortensi A; Unit of General Microsurgery and Hand Surgery, University of Rome 'La Sapienza' and Hospital 'Fabia Mater', Rome, Italy., D'Orazi V; Unit of General Microsurgery and Hand Surgery, University of Rome 'La Sapienza' and Hospital 'Fabia Mater', Rome, Italy., Panunzi A; Unit of General Microsurgery and Hand Surgery, University of Rome 'La Sapienza' and Hospital 'Fabia Mater', Rome, Italy., Milone P; Department of Medical and Surgical Sciences and Advanced Technologies 'G. Ingrassia', Section of Radiology, University of Catania, Catania, Italy., Maiolino L; Department of Medical and Surgical Sciences and Advanced Technologies 'G. Ingrassia', Section of Otolaryngology, University of Catania, Catania, Italy., Nicita F; Department of Paediatrics and Child Neuropsychiatry, Section of Paediatric Neurology, Sapienza University of Rome, Rome, Italy., Capone GL; Department of Biomedical, Experimental and Clinical Sciences 'Mario Serio', Section of Medical Genetics, University of Florence, Florence, Italy., Sestini R; Department of Biomedical, Experimental and Clinical Sciences 'Mario Serio', Section of Medical Genetics, University of Florence, Florence, Italy., Paganini I; Department of Biomedical, Experimental and Clinical Sciences 'Mario Serio', Section of Medical Genetics, University of Florence, Florence, Italy., Muglia M; 11 Unit of Molecular Genetics, Institute of Neurological Sciences, National Research Council, Cosenza, Italy., Cavallaro S; 11 Unit of Molecular Genetics, Institute of Neurological Sciences, National Research Council, Cosenza, Italy., Lanzafame S; Department of Medical and Surgical Sciences and Advanced Technologies 'G. F. Ingrassia', Section of Anatomic Pathology, University of Catania, Catania, Italy., Papi L; Department of Biomedical, Experimental and Clinical Sciences 'Mario Serio', Section of Medical Genetics, University of Florence, Florence, Italy., Ruggieri M; Unit of Rare Diseases of the Nervous System in Childhood, Department of Clinical and Experimental Medicine, Section of Pediatrics and Child Neuropsychiatry, University of Catania, AOU 'Policlinico-Vittorio Emanuele', Via S. Sofia, 78, 95124, Catania, Italy. m.ruggieri@unict.it.
Jazyk: angličtina
Zdroj: Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery [Childs Nerv Syst] 2017 Jun; Vol. 33 (6), pp. 933-940. Date of Electronic Publication: 2017 Apr 01.
DOI: 10.1007/s00381-017-3340-2
Abstrakt: Background: The INI1/SMARCB1 gene protein product has been implicated in the direct pathogenesis of schwannomas from patients with one form of schwannomatosis [SWNTS1; MIM # 162091] showing a mosaic pattern of loss of protein expression by immunohistochemistry [93% in familial vs. 55% in sporadic cases].
Aim of Study: To verify whether such INI1/SMARCB1 mosaic pattern could be extended to all schwannomas arising in the sporadic and familial schwannomatoses [i.e. to SMARCB1-related (SWNTS1) or LZTR1-related (SWNTS2) schwannomatosis or to SMARCB1/LZTR1-negative schwannomatosis] and whether it could be involved in classical NF2 or solitary peripheral schwannomas METHODS: We blindly analysed schwannoma samples obtained from a total of 22 patients including (a) 2 patients (2 males; aged 38 and 55 years) affected by non-familial SMARCB1-associated schwannomatosis (SWTNS1); (b) 1 patient (1 female; aged 33 years) affected by familial schwannomatosis (SWTNS1/ SMARCB1 germ line mutations); (c) 5 patients (3 males, 2 females; aged 33 to 35 years) affected by non-familial (sporadic) LZTR1-associated schwannomatosis (SWNTS2); (d) 3 patients (3 males; aged 35 to 47 years) affected by familial schwannomatosis (SWTNS2/ LZTR1 germ line mutations); (e) 2 patients (1 male, 1 female; aged 63 and 49 years, respectively) affected by non-familial schwannomatosis (SWTNS, negative for SMARCB1, LZTR1 and NF2 gene mutations); (f) 4 patients (3 males, 1 females; aged 15 to 24 years) affected by classical NF2 (NF2: harbouring NF2 germ line mutations; and (g) 5 patients (3 males, 2 females; aged 33 to 68 years) who had solitary schwannomas. [follow-up = 15-30 years; negative for constitutional/somatic mutation analysis for the SMARCB1, LZTR1 and NF2 genes] were (blindly) analyzed. The INI1/SMARCB1 immunostaining pattern was regarded as (1) diffuse positive nuclear staining [= retained expression] or (2) mosaic pattern [mixed positive/negative nuclei = loss of expression in a subset of tumour cells].
Results: All solitary peripheral schwannomas and NF2-associated vestibular schwannomas showed diffuse nuclear INI1/SMARCB1 staining in 97-100% of neoplastic cells; schwannomas obtained from all cases of non-familial and familial schwannomatosis and NF2-associated non-vestibular schwannomas showed a mosaic pattern ranging from 10 to 70% of INI1/SMARCB1-positive expression. We did not record a complete lack of nuclear staining.
Conclusions: The present data suggests that (a) mosaic loss of immunohistochemical INI1/SMARCB1 expression, despite the interlesional variability, is a reliable marker of schwannomatosis regardless of the involved gene and it might help in the differential diagnosis of schwannomatosis vs. solitary schwannomas and (b) INI1/SMARCB1 expression is not useful in the differential with mosaic NF2, since NF2-associated peripheral schwannomas show the same immunohistochemical pattern.
Databáze: MEDLINE
Externí odkaz: