Immunohistochemical examination of the expression of O6-methylguanine-DNA methyltransferase in human melanoma metastases

In tumour cell lines, an inverse relationship has been shown between susceptibility to the cytotoxic effects of the O 6-alkylating agents and the expression of the DNA repair protein O 6-methylguanineDNA methyltransferase (MGMT). One of the most effective single agents in chemotherapy of metastatic...

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Bibliographic Details
Published in:European journal of cancer (1990) 1997, Vol.33 (1), p.129-134
Main Authors: Egyházi, S., Margison, G.P., Hansson, J., Ringborg, U.
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Antineoplastic agents
Antineoplastic Agents - therapeutic use
Biological and medical sciences
Cell Division
Cell Nucleus - enzymology
Chemotherapy
Dacarbazine - therapeutic use
DNA repair
Female
Humans
Immunoenzyme Techniques
immunohistochemistry
Lymphatic Metastasis
Male
Medical sciences
Medicin och hälsovetenskap
melanoma
Melanoma - drug therapy
Melanoma - enzymology
Melanoma - secondary
Methyltransferases - metabolism
Middle Aged
O-Methylguanine-DNA Methyltransferase
O6-methylguanine-DNA methyltransferase
Pharmacology. Drug treatments
Skin Neoplasms - drug therapy
Skin Neoplasms - enzymology
Skin Neoplasms - secondary
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Summary:In tumour cell lines, an inverse relationship has been shown between susceptibility to the cytotoxic effects of the O 6-alkylating agents and the expression of the DNA repair protein O 6-methylguanineDNA methyltransferase (MGMT). One of the most effective single agents in chemotherapy of metastatic melanoma is the O 6-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).
ISSN:0959-8049
1879-0852
DOI:10.1016/S0959-8049(96)00342-5