Source: Annual Congress 2002 - Thoracic oncology: biology
Disease area: Thoracic oncology

Abstract

Purpose: Differentiating malignant from benign coin lesions is a common clinical problem. New molecular markers in endobronchial specimens are promising tools that could increase diagnostic sensitivity. Epigenetic silencing of the tumor suppressor gene p16(INK4a) (p16) and the DNA repair gene O6-Methylguanine DNA Methyltransferase (MGMT) by promoter hypermethylation is a common and early event in the multistep process leading to invasive cancer. The goal of this study was to investigate whether the assessment of such epigenetic changes in brush biopsies and bronchial washings could increase the diagnostic yield in cases of suspected peripheral lung carcinomas.
Method: Material was obtained using fluoroscopically guided protected brush biopsies and performing a bronchial lavage (10 ml) in the same bronchial segment.After DNA extraction by standard methods, we performed a bisulfite modification using a commercially available Kit followed by a methylation specific PCR (MSP).
Results: In 26 of 35 patients surgery proved a malignancy (adeno 10, squamous cell 7, large cell 4, small cell carcinoma O, others 5).
Hypermethylation of p16 and/or MGMT was found in 11/26 (42%), of p16 alone in 6/26 (23%) and of MGMT alone in 7/26 (27%).The correct diagnosis of malignancy could be established by cytological examination alone in only 10/26 cases (38%). Combining both methods allowed a correct diagnosis in 16/26 (62%).
Conclusion: We could show that using a protected brush for biopsy and bronchial lavage and combining standard cytological examination with detection of epigenetic phenomena as promoter hypermethylation of p16 and MGMT increases the diagnostic yield in small, peripherally located tumors.

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Citations should be made in the following way:
P. Litterst, L. Freitag, B. Obertrifter (Hemer, Germany). Detection of aberrant methylation of p16(INK4a) and MGMT in endobronchial specimens increases the diagnostic yield in cases of suspected peripheral lung carcinomas. Eur Respir J 2002; 20: Suppl. 38, 137

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