The Significance of Immunohistochemical Expression of Merlin, Ki-67, and p53 in Meningiomas

Abstract

Meningiomas are one of the most common CNS tumors whose appearance is closely linked to NF2 gene product merlin. Tumor markers Ki-67 and p53 play established role in tumor progression which should be analyzed in close association with merlin expression. The aim of this study was to investigate the immunohistochemical expression of merlin in meningiomas, correlation with Ki-67 and p53, and to determine the association of these results with histologic grade and subtype. The histologic sections of 170 patients with totally resected meningiomas, between January 2000 and December 2010, were classified according to WHO, immunohistochemically stained for Ki-67, p53, and merlin, and analyzed using light microscope. Ki-67 median was 5.6 times higher in group of patients with negative merlin than in those with positive merlin (P=0.05). Statistically significant correlation of merlin with p53 was found (P<0.001). Merlin expression between 2 combined groups (meningothelial/secretory and fibroblastic/transitional) was statistically significant (P=0.002). By comparing merlin expression and p53 levels, statistically significant difference was found (P=0.017). In the group with positive merlin and negative p53 as well as positive merlin and low p53, meningothelial/secretory subtypes of meningiomas were more common. In combination of negative merlin and negative p53 as well as negative merlin and high p53, there were more meningiomas of fibroblastic/transitional subtype. There was no statistically significant correlation between merlin and tumor grade (P=0.420). There is undeniable influence of merlin on the development and the proliferative ability of meningioma subtypes. Significant role of p53 pathway was confirmed.

Meningiomas em cães: aspectos clínicos, histopatológicos e imuno-histoquímicos

“…Resultados similares foram relatados em cães com neoplasias intracranianas (Violin 2009), sugerindo que nos cães não há expressão de p53 nas células neoplásicas dos meningiomas. Alterações na expressão de p53 são observadas nos meningiomas em humanos (Pavelin et al 2014), no entanto em animais há poucos dados sobre a expressão de p53 em neoplasmas (Koltai & Vajdovich 2014).…”

“…Dados sobre causas de neoplasias cerebrais são escassos na literatura. No homem observou-se que em meningiomas frequentemente ocorre inativação do gene de supressão tumoral Merlim, resultando em falhas no controle do crescimento e motilidade celular (Pavelin et al 2014).…”

“…A expressão da proteína p53, responsável pela regulação do ciclo celular e apoptose, também é utilizada como fator prognóstico (Schmitt 1999). Recentemente verificou-se que meningiomas humanos com maior expressão de Ki-67 e p53 estavam associados à inativação do gene Merlim (Pavelin et al 2014). Em cães, constatou-se que, utilizando o anticorpo anti-Ki-67, o índice proliferativo médio nos meningiomas foi de 5,7%.…”

Prognostic Value of Ki-67 Labeling Index and Postoperative Radiotherapy in WHO Grade II Meningioma

“…The prognostic significance of other tumor markers, such as antiphosphohistone, merlin, p53, or PCNA could be investigated in further studies. [33][34][35] CONCLUSIONS Ki-67 LI is not only a clinically but also histologically useful prognostic marker in WHO grade II meningiomas. Ki-67 LI is a reasonably applicable marker for predicting local treatment outcomes in meningiomas, and moreover, PORT should be recommended in WHO grade II meningioma patients with Ki-67 LIs > 13%.…”

Molecular Targets and Treatment of Meningioma

“…Different types of meningiomas have shown varying levels of merlin loss, which may explain a change in treatment paradigm for the varying subsets of meningioma. Meningothelial meningiomas tend to express lower levels of merlin loss than fibrous and other forms of meningiomas [14].…”