Merlin expression in secretory meningiomas: evidence of an NF2-independent pathogenesis? Immunohistochemical study.

One of the most common chromosomal regions implicated in the meningiomas tumorigenesis is 22q12 where the neurofibromatosis 2 (NF2) gene resides. The NF2 tumor-suppressor gene encodes for the merlin/schwannomin protein, which is responsible for the inherited disease neurofibromatosis 2. NF2 gene mutations predominantly occur in transitional and fibroblastic meningiomas, whereas the meningothelial variant is less affected. Secretory meningioma is an infrequent meningioma subtype. Its most typical morphologic feature is the presence of intracytoplasmic or extracytoplasmic round hyaline, eosinophilic, and periodic acid Shiff-positive bodies in a lesion frequently otherwise classifiable as meningothelial meningioma. This study reviews the immunohistochemical merlin expression in 14 consecutive secretory meningiomas. Our purpose was to investigate if secretory meningiomas, analogous to meningothelial meningiomas, follow a molecular route of pathogenesis independent of the neurorofibromatosis 2 gene-associated pathway. All meningiomas showed positive immunocoloration involving the majority of the hyaline inclusions and secretory cells; in 12 (86%) meningiomas, a positive immunoreaction was also documented in nonsecretory tumoral cells. Our results may indicate a molecular, besides morphologic, similarity between secretory and meningothelial meningiomas: the almost constant merlin immunohistochemical expression in our series gives evidence for a possible NF2 gene-independent pathogenesis in secretory meningiomas.

Cyclooxygenase-2 (COX-2) overexpression in meningiomas: real time PCR and immunohistochemistry.

Cyclooxygenase-2 (COX-2) is the inducible form of the enzyme involved in the first steps of the prostaglandins and thromboxane synthesis. COX-2 up-regulation is demonstrated in tumors where it can modulate tumoral progression, metastasis, multidrug resistance, and angiogenesis. Experimental data suggest a possible therapeutic use of the COX-inhibitors nonsteroidal antiinflammatory drugs (NSAIDs). NSAIDs can block tumor growth through many mechanisms, especially through antiangiogenic and proapoptotic effects. Moreover, NSAIDs can also improve the efficacy of radiotherapy, chemotherapy, and hormonal therapy. This study reviews the COX-2 expression as evaluated through immunohistochemistry and real time polymerase chain reaction (RT-PCR) in 23 meningiomas [14 World Health Organization (WHO) grade I; 5 WHO grade II; 3 WHO grade III; 1 oncocytic meningioma]. At immunohistochemistry all the lesions but 4 (83%) were COX-2 positive. At RT-PCR 9 meningiomas, 8 WHO grade I and 1 WHO grade II, showed a COX-2 expression greater than the reference value (average expression of all meningiomas that we studied). The association between tumor grade and immunohistochemical or RT-PCR COX-2 expression was not significant (P=0.427 and P=0.251, respectively). In conclusion, even if further studies on larger series are necessary, the common COX-2 overexpression in meningiomas may suggest considering the COX-2 inhibitors, alone or in combination with radiotherapy, a potential area of therapeutic intervention in some selected meningiomas.

Cyclooxygenase-2 in oligodendroglioma: possible prognostic significance.

Cyclooxygenase-2 (COX-2) is the inducible form of the enzyme involved in the first two steps of the prostaglandins and thromboxane synthesis. Up-regulation of COX-2 is demonstrated in tumors where it can modulate tumoral progression, metastasis, multidrug resistance and angiogenesis. Selective COX-2 inhibitors are seen with growing interest in the tumors treatment. This present study reviews the COX-2 expression in 32 primary oligodendrogliomas (24 WHO II; eight WHO III) and two glioblastomas with prominent oligodendroglial features (WHO IV). Immunohistochemical results were compared with survival in order to verify the COX-2 prognostic significance. COX-2 positivity was found in 44% tumors. Median survival of the patients with a COX-2 positive lesion was 37 months; median survival of the patients with a COX-2 negative lesion was 93 months (P =0.010). Twenty-nine percent WHO grade II tumors, 87% WHO grade III, 50% WHO grade IV resulted COX-2 positive (P =0.016). In patients affected by WHO grade II oligodendroglioma, median survival was 24 and 96 months, respectively, in COX-2 positive and negative lesions (P =0.012). In conclusion, even if further studies on different, homogeneous and larger series in vivo are certainly necessary, it is believed that COX-2 could really have a prognostic value and can be considered as a possible therapeutic opportunity.