TY - JOUR
T1 - Frequency of O6-methylguanine-DNA methyltransferase promoter methylation in cytological samples from small cell lung cancer
AU - Miglio, Umberto
AU - Mezzapelle, Rosanna
AU - Paganotti, Alessia
AU - Veggiani, Claudia
AU - Mercalli, Francesca
AU - Mancuso, Giuseppe
AU - Gaudino, Erica
AU - Rena, Ottavio
AU - Buosi, Roberta
AU - Boldorini, Renzo
PY - 2015/11/1
Y1 - 2015/11/1
N2 - 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.
AB - 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.
KW - alkylating agents
KW - cytology
KW - methylation analysis
KW - methylguanine-DNA methyltransferase
KW - small cell lung cancer
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U2 - 10.1002/dc.23319
DO - 10.1002/dc.23319
M3 - Article
C2 - 26152836
AN - SCOPUS:84944167171
VL - 43
SP - 947
EP - 952
JO - Diagnostic Cytopathology
JF - Diagnostic Cytopathology
SN - 8755-1039
IS - 11
ER -