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 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).
Egyházi
S
S
Department of Oncology, Karolinska Hospital, Stockholm, Sweden.
Margison
G P
GP
Hansson
J
J
Ringborg
U
U
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002455:Cell Division; D002467:Cell Nucleus / Q000201:enzymology; D003606:Dacarbazine / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000201:enzymology* / Q000556:secondary*; D008780:Methyltransferases / Q000378:metabolism*; D008875:Middle Aged; D019853:O(6)-Methylguanine-DNA Methyltransferase; D012878:Skin Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000556:secondary
D000970:Antineoplastic Agents; D003606:Dacarbazine; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase