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

Diagn Cytopathol. 2015 Nov;43(11):947-52. doi: 10.1002/dc.23319. Epub 2015 Jul 7.

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%).

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.

Keywords: alkylating agents; cytology; methylation analysis; methylguanine-DNA methyltransferase; small cell lung cancer.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biopsy, Fine-Needle / methods
  • DNA Methylation / physiology*
  • Dacarbazine / analogs & derivatives
  • Dacarbazine / pharmacology
  • Glioma / diagnosis
  • Glioma / pathology*
  • Guanine / analogs & derivatives*
  • Guanine / pharmacology
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / diagnosis
  • Neoplasm Recurrence, Local / pathology*
  • O(6)-Methylguanine-DNA Methyltransferase
  • Promoter Regions, Genetic / genetics*
  • Small Cell Lung Carcinoma / diagnosis
  • Small Cell Lung Carcinoma / pathology*
  • Temozolomide

Substances

  • Guanine
  • Dacarbazine
  • O-(6)-methylguanine
  • O(6)-Methylguanine-DNA Methyltransferase
  • Temozolomide