Artikel
hTERT promoter methylation in meningeal tumors correlates independently with histopathological subtype, WHO grading and clinical factors, but not with prognosis
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Autoren
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Gina Fürtjes
- Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Münster, Deutschland
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Martin Hasselblatt
- Institut für Neuropathologie, Universitätsklinikum Münster, DeutschlandThis research was funded by the Deutsche Gesellschaft für Neurochirurgie, "Stiftung neurochirugische Forschung".
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Werner Paulus
- Institut für Neuropathologie, Universitätsklinikum Münster, DeutschlandThis research was funded by the Deutsche Gesellschaft für Neurochirurgie, "Stiftung neurochirugische Forschung".
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Walter Stummer
- Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Münster, Deutschland
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Susanne Peetz-Dienhart
- Institut für Neuropathologie, Universitätsklinikum Münster, DeutschlandThis research was funded by the Deutsche Gesellschaft für Neurochirurgie, "Stiftung neurochirugische Forschung".
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Benjamin Brokinkel
- Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Münster, Deutschland
| Veröffentlicht: | 2. Juni 2015 |
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Gliederung
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Objective: Telomerase (TERT) expression is observed in >90% of malignant tumors and is highly correlated to methylation and hotspot mutations of the h(human)TERT promoter. However, hTERT promoter mutations have been rarely observed in the vast majority of malignant meningeal tumors. Here, we provide an analysis of promoter methylation in a large group of grade II and III meningiomas (ME) and hemangiopericytomas (HPC).
Method: DNA of 93 tumors including 55 ME and 38 HPC (N=93) was isolated from formalin-fixed paraffin-embedded tissue samples and transferred to methylation-specific PCR.
Results: Samples included 22 primary ME (5°II and 17°III) and 33 HPC (25°II and 8°III) as well as 33 recurrent ME (7°II and 26°III) and 5 HPC (1°II and 4°III). In summary the incidence of methylation (61%) was higher in ME than in HPC (N=47/55, 86% and N=10/38, 26%, respectively, p<.01), higher in °II than in °III tumors (N=16/38, 42% vs. N=41/55, 75%, respectively, p=.02) and higher in recurrent (87%, N=33/38) than in primary diagnosed tumors (44%, N=24/55; p<.01). Patients with promoter methylation were significantly older than non-methylated individuals (66 vs. 55 years, median, p=.002). Multivariat analyses confirmed increased methylation in ME (p<0.01), recurrences (p=.014) and older patients (p=.017). In ME, promoter methylation was found in 86% (N=47) distributed to 10 of 12°II (83%) and 37 of 43°III (86%) tumors. In uni- and multivariat analyses, methylation was independent of patients' age and sex but significantly more frequent in recurrent (94%, N=31/33) than in primary diagnosed tumors (73%, N=16/22; p=.044). In HPC the incidence of promoter methylation was similar in primary and recurrent tumors and independent of sex, age, WHO grade and metastasis. Median follow-up was available in 13 of 22 patients with ME and 25 of 33 patients with HPC with a median follow-up of 29 (range 0-180) and 37 months (range 0-176), respectively. With a median progression-free survival (PFS) of 12 and 37 months, recurrence occurred in 10 patients (77%) with ME and 10 (40%) with HPC. In ME and HPC, the mortality, progression rates, overall survival and PFS were independent of promoter methylation in uni- and multivariate analyses.
Conclusions: hTERT promoter methylation is frequent in meningeal tumors but varies widely among different subtypes, WHO grades and between primary tumors and recurrences. Although strongly correlated to clinical features, methylation is independent of patients' prognosis.
