Frequency of O6-methylguanine-DNA methyltransferase promoter methylation in cytological samples from small cell lung cancer

Umberto Miglio, Rosanna Mezzapelle, Alessia Paganotti, Claudia Veggiani, Francesca Mercalli, Giuseppe Mancuso, Erica Gaudino, Ottavio Rena, Roberta Buosi, Renzo Boldorini

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)947-952
Number of pages6
JournalDiagnostic Cytopathology
Volume43
Issue number11
DOIs
Publication statusPublished - Nov 1 2015

Fingerprint

Small Cell Lung Carcinoma
Methyltransferases
Methylation
DNA
temozolomide
Fine Needle Biopsy
Sputum
Biopsy
Fixatives
Alkylating Agents
Astrocytoma
Glioma
Formaldehyde
Brazil
O-(6)-methylguanine
Neoplasms
Cell Count
Polymerase Chain Reaction
Genes

Keywords

  • alkylating agents
  • cytology
  • methylation analysis
  • methylguanine-DNA methyltransferase
  • small cell lung cancer

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology

Cite this

Miglio, U., Mezzapelle, R., Paganotti, A., Veggiani, C., Mercalli, F., Mancuso, G., ... Boldorini, R. (2015). Frequency of O6-methylguanine-DNA methyltransferase promoter methylation in cytological samples from small cell lung cancer. Diagnostic Cytopathology, 43(11), 947-952. https://doi.org/10.1002/dc.23319

Frequency of O6-methylguanine-DNA methyltransferase promoter methylation in cytological samples from small cell lung cancer. / Miglio, Umberto; Mezzapelle, Rosanna; Paganotti, Alessia; Veggiani, Claudia; Mercalli, Francesca; Mancuso, Giuseppe; Gaudino, Erica; Rena, Ottavio; Buosi, Roberta; Boldorini, Renzo.

In: Diagnostic Cytopathology, Vol. 43, No. 11, 01.11.2015, p. 947-952.

Research output: Contribution to journalArticle

Miglio, U, Mezzapelle, R, Paganotti, A, Veggiani, C, Mercalli, F, Mancuso, G, Gaudino, E, Rena, O, Buosi, R & Boldorini, R 2015, 'Frequency of O6-methylguanine-DNA methyltransferase promoter methylation in cytological samples from small cell lung cancer', Diagnostic Cytopathology, vol. 43, no. 11, pp. 947-952. https://doi.org/10.1002/dc.23319
Miglio, Umberto ; Mezzapelle, Rosanna ; Paganotti, Alessia ; Veggiani, Claudia ; Mercalli, Francesca ; Mancuso, Giuseppe ; Gaudino, Erica ; Rena, Ottavio ; Buosi, Roberta ; Boldorini, Renzo. / Frequency of O6-methylguanine-DNA methyltransferase promoter methylation in cytological samples from small cell lung cancer. In: Diagnostic Cytopathology. 2015 ; Vol. 43, No. 11. pp. 947-952.
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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.",
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