Immunohistochemical examination of the expression of O6-methylguanine-DNA methyltransferase in human melanoma metastases.
AffiliationDepartment of Oncology, Karolinska Hospital, Stockholm, Sweden.
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AbstractIn tumour cell lines, an inverse relationship has been shown between susceptibility to the cytotoxic effects of the O6-alkylating agents and the expression of the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT). One of the most effective single agents in chemotherapy of metastatic melanoma is the O6-alkylating drug, dacarbazine. We therefore examined the distribution of MGMT in 37 skin and lymph node melanoma metastases using rabbit antihuman MGMT antiserum. MGMT expression was undetectable in tumours from 2 out of 34 patients and low in 4 further patients. When present, staining was mainly nuclear and showed a marked variation both among tumour cells within the same metastases, between separate metastases in the same patient and between tumours in different patients. MGMT expression determined by immunohistochemistry showed a relation to MGMT activity measurements, but was not related to the number of proliferating cells, as identified by staining with MIB-1 antibody. Tumour cells with moderate to strong immunostaining with MGMT antiserum were significantly more abundant in metastases excised after dacarbazine-based chemotherapy (n = 8) than in those excised before treatment (n = 29).
CitationImmunohistochemical examination of the expression of O6-methylguanine-DNA methyltransferase in human melanoma metastases. 1997, 33 (1):129-34 Eur. J. Cancer
JournalEuropean Journal of Cancer
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