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Her2neu Amplification Associates with Co-deletion 1p/14q in Recurrent Meningiomas

Published online by Cambridge University Press:  23 September 2014

Brenda O. Hamilton*
Affiliation:
Department of Molecular Pathology, London Health Science Center, London, Ontario, Canada
Joanne S. Sy
Affiliation:
Department of Neuropathology, University of Sydney, NSW 2006, Australia
Joseph F. Megyesi
Affiliation:
Department of Clinical Neurosciences, London Health Science Center, London, Ontario, Canada
Lee Cyn Ang
Affiliation:
Department of Neuropathology, London Health Science Center, London, Ontario, Canada
*
Molecular Pathology, London Health Science Center, Victoria Hospital, 800 Commissioners Rd E, London, Ontario, N6A 5W9, Canada. Email: [email protected]
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Abstract

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Background:

The current methods to predict recurrence and aggressive behaviour of meningiomas rely mainly on histological grading, histological subtype, proliferative index, as well as brain invasion. In many instances, histological grade alone fails to predict recurrence in the grade I and grade II meningiomas. Deletions of 1p and 14q have previously been reported to correlate with poor prognosis in terms of either recurrence or higher histological grades. The Her2neu (ErbB2) amplification has been shown to be a useful predictor of aggressive behaviour in breast and ovarian tumours, but its significance in meningioma is so far uncertain.

Method:

In order to determine the cytogenetic differences between 22 recurrent and 25 non-recurrent meningiomas of all grades, we used fluorescent in situ hybridization (FISH) DNA probes for 1p36, 14q11.2 and 17q11.2-12 (Her2neu) on formalin fixed paraffin embedded (FFPE) tissue from the Brain Tumour Tissue Bank (BTTB), London Health Science Center (LHSC).

Results:

We showed a positive association for meningioma recurrence correlated with 1p36 deletion plus or minus 14q 11.2 deletions in all grades of meningiomas. The Her2neu amplification was strongly associated with 1p/14q co-deletion in cases of recurrent meningiomas, especially the higher grade tumours.

Conclusion:

These cytogenetic markers can be applied in addition to histological grading for predicting the risk of recurrence and biological behaviour.

Résumé:

Résumé:Contexte:

Les méthodes actuelles pour prédire une récidive et un comportement agressif des méningiomes sont fondées principalement sur le grade histologique de la tumeur, son sous-type histologique, l'indice de prolifération et l'envahissement de la tumeur. Dans plusieurs cas, le grade histologique seul ne prédit pas la récidive dans les méningiomes de grade I et de grade II. Des délétions 1p et 14q ont été rapportées antérieurement comme étant corrélées à un mauvais pronostic en ce qui concerne la récidive ou à un grade histologique supérieur. Il a été démontré que l'amplification de Her2neu (ErbB2) est un facteur de prédiction utile d'un comportement tumoral agressif dans les tumeurs du sein et de l'ovaire, mais sa signification dans le méningiome demeure incertaine.

Méthode:

Nous avons utilisé l'hybridisation in situ avec sonde fluorescente d'ADN (FISH) des régions 1p36, 14q11,2 et 17q11,2-12 (Her2neu) sur du tissu inclus dans la paraffine provenant de la Brain Tumour Tissue Bank (BTTB) du London Health Science Center.

Résultats:

Nous avons démontré qu'il existe une association positive entre la récidive du méningiome et une délétion 1p36 plus ou moins 14q11,2 quelque soit le grade du méningiome. L'amplification de Her2neu était fortement associée à une co-délétion 1p/14q dans les cas de méningiomes récurrents, spécialement pour les tumeurs de plus hauts grades.

Conclusion:

Ces marqueurs cytogénétiques peuvent êtres utilisés comme complément de la classification de la tumeur pour prédire le risque de récidive et le comportement biologique de la tumeur.

Type
Research Article
Copyright
Copyright © The Canadian Journal of Neurological 2013

References

1. Perry, A, Gutmann, DH, Reifenberger, G. Molecular pathogenesis of meningiomas. J Neurooncol. 2004;70:183202.Google Scholar
2. Perry, A, Louis, DN, Scheithauver, BW, Budka, H, von Deimling, A. Meningeal tumours. In: WHO Classification of tumours of the central nervous system. Louis, DN, Ohgaki, H, Wiestler, OD, Cavenee, WK, editors. 4th ed. Lyon, France: IARC Press, 2007. p. 163–72.Google Scholar
3. Pfisterer, WK, Hendricks, WP, Scheck, AC, et al. Fluorescent in situ hybridization and ex vivo 1H magnetic resonance spectroscopic examinations of meningioma tumor tissue: is it possible to identify a clinically-aggressive subset of benign meningiomas? Neurosurgery. 2007;61:1048–61.Google Scholar
4. Al-Mefty, O, Kadri, PAS, Pravdenkova, S, Sawyer, JR, Stangeby, C, Husain, M. Malignant progression in meningioma: documentation of a series and analysis of cytogenetic findings. J Neurosurg. 2004;101:210–18.Google Scholar
5. Cai, DX, Banerjee, R, Scheithauer, BW, Lohse, CM, Kleinschmidt-DeMasters, BK, Perry, A. Chromosome 1p and 14q FISH analysis in clinicopathologic subsets of meningioma: diagnostic and prognostic implication. J Neuropathol Exp Neurol. 2001;60:628–36.Google Scholar
6. Maillo, A, Orfao, A, Espinosa, AB, et al. Early recurrences in histologically benign/grade l meningiomas are associated with large tumors and coexistence of monosomy 14 and del (1p36) in the ancestral tumor cell clone. Neuro Oncol. 2007;9:438–46.Google Scholar
7. Buschges, R, Ichimura, K, Weber, RG, Reifenberger, G, Collins, VP. Allelic gain and amplification on the long arm of chromosome 17 in anaplastic meningiomas. Brain Pathol. 2002;12:145–53.Google Scholar
8. Jansen, M, Mohapatra, G, Betensky, RA, Keohane, C, Louis, DN. Gain of chromosome arm 1q in atypical meningioma correlates with shorter progression-free survival. Neuropathol Appl Neurobiol. 2012;38:213–19.Google Scholar
9. Slamon, DJ, Clark, GM, Wong, SG. Human breast cancer: correlation of relapse and survival with amplification of the Her-2/neu oncogene. Science. 1987; 235:177–82.Google Scholar
10. Loussouarn, D, Brunon, J, Avet-Loiseau, H, Campone, M, Mosnier, JF. Prognostic value of Her2 expression in meningiomas: an immunohistochemical and fluorescence in situ hybridization study. Hum Pathol. 2006;37:415–21.Google Scholar
11. Ozer, O, Sahin, FI, Aydemir, F, Ozen, O, Yilmaz, Z, Altinors, N. Her2/neu gene amplification in paraffin-embedded tissue sections of meningioma patients. Turk Neurosurg. 2009;19:135–8.Google Scholar
12. Pfisterer, WK, Hank, NC, Preul, MC, et al. Diagnostic and prognostic significance of genetic regional heterogeneity in meningiomas. Neuro Oncol. 2004;6:290–9.Google Scholar
13. Andersson, U, Guo, D, Malmer, B, et al. Epidermal growth factor receptor family (EGFR, ErbB2-4) in gliomas and meningiomas. Acta Neuropathol. 2004;108:135–42.Google Scholar
14. Chozick, BS, Benzil, DL, Stopa, EG, et al. Immunohistochemical evaluation of erbB-2 and p53 protein expression in benign and atypical human meningiomas. J Neurooncol. 1996;27:117–26.Google Scholar
15. Schlegel, J, Ulrich, B, Stumm, G, et al. Expression of the c-erbB-2-encoded oncoprotein and progesterone receptor in human meningiomas. Acta Neuropathol. 1993;86:473–9.Google Scholar
16. Abdelzaher, E, El-Gendi, SM, Yehya, A, Gowil, AG. Recurrence of benign meningiomas: predictive value of proliferative index, BCL2, p53, hormonal receptors and HER2 expression. Br J Neurosurg. 2011;25:707–13.Google Scholar
17. Wang, CL, Mei, JH, Wang, SS, Xu, S, Xu, LL, Xiong, YF. Expression of HER2/neu in meningiomas: an immunohistochemistry and fluorescence in situ hybridization study. [Zhonghua Bing Li Xue Za Zhi] Chin J Pathol. 2010;39:156–60.Google Scholar
18. Laurendeau, I, Ferrer, M, Garrido, D, et al. Gene expression profiling of ErbB receptors and ligands in human meningiomas. Cancer Invest. 2009;27:691–8.Google Scholar
19. Gradishar, WJ. Her 2 therapy -an abundance of riches. N Engl J Med. 2012;366:176–8.Google Scholar
20. Ammoun, S, Cunliffe, CH, Allen, JC, et al. ErbB/HER receptor activation and preclinical efficacy of lapatinib in vestibular schwannoma. Neuro Oncol. 2010;12:834–43.Google Scholar