title: Frequency of O⁶-methylguanine-DNA methyltransferase promoter methylation in cytological samples from small cell lung cancer.
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 O(6) -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%).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Unit of Pathology, Department of Health Sciences, University of Eastern Piedmont "Amedeo Avogadro", Novara, 28100, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Miglio
authors.affiliation: Unit of Pathology, Department of Health Sciences, University of Eastern Piedmont "Amedeo Avogadro", Novara, 28100, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Mezzapelle
authors.affiliation: Division of Pathology, "Maggiore Della Carità" Hospital, Novara, 28100, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Paganotti
authors.affiliation: Division of Pathology, "Maggiore Della Carità" Hospital, Novara, 28100, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Veggiani
authors.affiliation: Unit of Pathology, Department of Health Sciences, University of Eastern Piedmont "Amedeo Avogadro", Novara, 28100, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Mercalli
authors.affiliation: Unit of Pathology, Department of Health Sciences, University of Eastern Piedmont "Amedeo Avogadro", Novara, 28100, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Mancuso
authors.affiliation: Division of Oncology, Department of Translational Medicine, University of Eastern Piedmont "Amedeo Avogadro", Novara, 28100, Italy.
authors.forename: Erica
authors.initials: E
authors.lastname: Gaudino
authors.affiliation: Division of Thoracic Surgery, "Maggiore Della Carità" Hospital, Novara, 28100, Italy.
authors.forename: Ottavio
authors.initials: O
authors.lastname: Rena
authors.affiliation: Division of Oncology, Department of Translational Medicine, University of Eastern Piedmont "Amedeo Avogadro", Novara, 28100, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Buosi
authors.affiliation: Unit of Pathology, Department of Health Sciences, University of Eastern Piedmont "Amedeo Avogadro", Novara, 28100, Italy.|Division of Pathology, "Maggiore Della Carità" Hospital, Novara, 28100, Italy.
authors.forename: Renzo
authors.initials: R
authors.lastname: Boldorini
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044963:Biopsy, Fine-Needle / Q000379:methods; D019175:DNA Methylation / Q000502:physiology*; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000494:pharmacology; D005910:Glioma / Q000175:diagnosis / Q000473:pathology*; D006147:Guanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000473:pathology*; D019853:O(6)-Methylguanine-DNA Methyltransferase; D011401:Promoter Regions, Genetic / Q000235:genetics*; D055752:Small Cell Lung Carcinoma / Q000175:diagnosis / Q000473:pathology*; D000077204:Temozolomide
chemical_list: D006147:Guanine; D003606:Dacarbazine; C008449:O-(6)-methylguanine; D019853:O(6)-Methylguanine-DNA Methyltransferase; D000077204:Temozolomide
keywords: alkylating agents; cytology; methylation analysis; methylguanine-DNA methyltransferase; small cell lung cancer