MGMT methylation assessment in glioblastoma: MS-MLPA versus human methylation 450K beadchip array and immunohistochemistry

Purpose: The MGMT gene encodes a DNA repair enzyme that counteracts with chemotherapy efficiency, specifically with alkylating agents such as temozolomide (TMZ). It is well established that MGMT methylation should be screened as a predictive marker for TMZ in glioblastoma, and we thus aimed to determine a reliable and practical diagnostic method of MGMT methylation detection. Patients and methods: 55 glioblastomas were investigated for MGMT methylation status using methylation-specific multiplexed ligation probe amplification (MS-MLPA), illumina human methylation 450K BeadChip array (HM450 K) analysis, and compared to MGMT protein expression by immunohistochemistry (IHC) staining. The methylation status of promoter, intron and all MGMT CpG targeted sites were separately correlated to patient’s survival. Results: In addition to MS-MLPA and 450 K concordance, our results showed significantly higher overall survival (OS) of patients receiving TMZ and presenting MGMT methylated promoter (mean OS = 21.5 months, p = 0.046). Including all glioblastoma cases and regardless of chemotherapy, MS-MLPA showed significant survival difference between MGMT methylated and unmethylated cases (mean OS = 13, p = 0.021). Conclusion: We concluded that in glioblastoma, MGMT promoter methylation predicts TMZ sensitivity. This current comparative analysis leads to consider that MS-MLPA is a valuable as HM450 K array for MGMT methylation status screening (AU)

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[Congenital pulmonary lymphangiectasis: an unusual cause of respiratory distress in neonates]. / Lymphangiectasies pulmonaires congénitales: une cause rare de détresse respiratoire néonatale.

Congenital pulmonary lymphangiectasis (CPL) is a rare condition in neonates characterized by abnormal dilatation of the lymphatics draining the interstitial and subpleural spaces of the lungs. Diagnosis is difficult in the neonatal period because respiratory features and radiological findings are not specific of the disease. Definitive diagnosis of CPL can be made only by pathologic examinations. We report a case of a male near-term neonate presenting with severe respiratory distress at birth. The initial chest X-ray showed frosted glass-like infiltrates with air bronchogram suggesting a maternofetal infection or respiratory distress syndrome. The infant required mechanical ventilation and chest tube insertion for right then bilateral pneumothorax. The child died 15 days later in spite of optimal high-frequency ventilation, bilateral pneumothorax drainage, and hemodynamic support. Autopsy revealed features consistent with the diagnosis of CPL. Although CPL is very rare, we should be aware that it is a possible cause of severe unexplained respiratory distress in neonates.