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Frequency of O6‐methylguanine‐DNA methyltransferase promoter methylation in cytological samples from small cell lung cancer
Authors:Umberto Miglio Ph.D  Rosanna Mezzapelle Ph.D  Alessia Paganotti B.Sc.  Claudia Veggiani B.Sc.  Francesca Mercalli M.D.  Giuseppe Mancuso M.Sc.  Erica Gaudino M.D.  Ottavio Rena Ph.D  Roberta Buosi M.D.  Renzo Boldorini M.D.
Affiliation:1. Unit of Pathology, Department of Health Sciences, University of Eastern Piedmont “Amedeo Avogadro”, Novara, Italy;2. Division of Pathology, “Maggiore Della Carità” Hospital, Novara, Italy;3. Division of Oncology, Department of Translational Medicine, University of Eastern Piedmont “Amedeo Avogadro”, Novara, Italy;4. Division of Thoracic Surgery, “Maggiore Della Carità” Hospital, Novara, Italy
Abstract:
Background. In a phase II study for patients with relapsed small cell lung cancer (SCLC), the administration of Temozolomide, an alkylating agent used in gliomas and anaplastic astrocytoma, showed a effective activity when O6‐methylguanine‐DNA methyltransferase (MGMT) gene promoter was methylated. Methods. We tested the feasibility of MGMT promoter status evaluation in small biopsies and cytological specimens routinely processed for diagnostic purposes. We tested samples from 56 patients with SCLC: 30 tissue biopsies, 17 fine‐needle aspiration biopsy, 8 bronchial washing, and 1 was a sputum. Biopsies and fine‐needle aspiration biopsy were fixed in formalin, bronchial washing and sputum in Dubosq Brazil. DNA was extracted after macrodissection of the areas containing the maximum number of cancer cells. MGMT promoter methylation status was assessed by methylation specific PCR. Results. Methylation analysis was obtained in 54 samples (54/56) and failed in two bronchial wash. MGMT promoter was methylated in 35.2% of the cases without any significant difference between histological and cytological samples (37.9% vs. 32%). Conclusion. MGMT promoter methylation is present in SCLC and cytological samples are perfectly adequate for methylation analysis, even if they were taken during routine diagnostic procedures, using different fixative and with low number and percentage of cancer cells. Diagn. Cytopathol. 2015;43:947–952. © 2015 Wiley Periodicals, Inc.
Keywords:small cell lung cancer  methylation analysis  alkylating agents  methylguanine‐DNA methyltransferase  cytology
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