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Child's Nervous System

, Volume 33, Issue 6, pp 933–940 | Cite as

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

  • Rosario Caltabiano
  • Gaetano Magro
  • Agata Polizzi
  • Andrea Domenico Praticò
  • Andrea Ortensi
  • Valerio D’Orazi
  • Andrea Panunzi
  • Pietro Milone
  • Luigi Maiolino
  • Francesco Nicita
  • Gabriele Lorenzo Capone
  • Roberta Sestini
  • Irene Paganini
  • Mariella Muglia
  • Sebastiano Cavallaro
  • Salvatore Lanzafame
  • Laura Papi
  • Martino RuggieriEmail author
Original Paper

Abstract

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.

Keywords

Schwannomatosis SWNTS Neurofibromatosis type 2 NF2 SMARCB1 LZTR1 INI1 Mosaicism Neurofibromatosis Histology Immunohistochemistry 

Notes

Compliance with ethical standards

Written informed consent was obtained from parents or guardians of all recruited individuals. The study was approved by the Ethical Committee [Catania 1], located at the University Hospital (AOU) “Policlinico-Vittorio Emanuele” in Catania, Italy.

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Rosario Caltabiano
    • 1
  • Gaetano Magro
    • 1
  • Agata Polizzi
    • 2
    • 3
  • Andrea Domenico Praticò
    • 4
    • 5
  • Andrea Ortensi
    • 6
  • Valerio D’Orazi
    • 6
  • Andrea Panunzi
    • 6
  • Pietro Milone
    • 7
  • Luigi Maiolino
    • 8
  • Francesco Nicita
    • 9
  • Gabriele Lorenzo Capone
    • 10
  • Roberta Sestini
    • 10
  • Irene Paganini
    • 10
  • Mariella Muglia
    • 11
  • Sebastiano Cavallaro
    • 11
  • Salvatore Lanzafame
    • 1
  • Laura Papi
    • 10
  • Martino Ruggieri
    • 4
    Email author
  1. 1.Department of Medical and Surgical Sciences and Advanced Technologies “G. F. Ingrassia”, Section of Anatomic PathologyUniversity of CataniaCataniaItaly
  2. 2.National Centre for Rare DiseasesIstituto Superiore di SanitàRomeItaly
  3. 3.Institute of Neurological SciencesNational Research CouncilCataniaItaly
  4. 4.Unit of Rare Diseases of the Nervous System in Childhood, Department of Clinical and Experimental Medicine, Section of Pediatrics and Child NeuropsychiatryUniversity of Catania, AOU “Policlinico-Vittorio Emanuele”CataniaItaly
  5. 5.Department of Biomedical and Biotechnological SciencesUniversity of CataniaCataniaItaly
  6. 6.Unit of General Microsurgery and Hand SurgeryUniversity of Rome “La Sapienza” and Hospital “Fabia Mater”RomeItaly
  7. 7.Department of Medical and Surgical Sciences and Advanced Technologies “G. Ingrassia”, Section of RadiologyUniversity of CataniaCataniaItaly
  8. 8.Department of Medical and Surgical Sciences and Advanced Technologies “G. Ingrassia”, Section of OtolaryngologyUniversity of CataniaCataniaItaly
  9. 9.Department of Paediatrics and Child Neuropsychiatry, Section of Paediatric NeurologySapienza University of RomeRomeItaly
  10. 10.Department of Biomedical, Experimental and Clinical Sciences “Mario Serio”, Section of Medical GeneticsUniversity of FlorenceFlorenceItaly
  11. 11.11 Unit of Molecular Genetics, Institute of Neurological SciencesNational Research CouncilCosenzaItaly

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