Immunohistochemical analysis of O(6)-methylguanine-DNA methyltransferase in human melanoma in comparison with skin squamous cell carcinoma.

Alkylating agents, often used for chemotherapy in patients with melanoma, can produce O(6)-alkylguanine (O(6)AG) which is related to tumor cell killing after treatment with alkylating agents. O(6)AG is effectively eliminated by O(6)-methylguanine-DNA methyltransferase (O(6)MGMT) and its level is correlative to the resistance to alkylating agents. However, little is known about the relationship of O(6)MGMT to the characteristics of melanoma. This study investigated the expression of O(6)MGMT in 12 melanomas and compared it with that in 11 skin squamous cell cancers (SCCs) immunohistochemically to evaluate the O(6)MGMT activity in melanoma and its clinical significance. All of the SCC samples had high O(6)MGMT expression, while the expression of O(6)MGMT in melanoma was diverse and 4 out of 12 samples had no or extremely low O(6)MGMT activity. Out of 6 lesions obtained from metastasis, 4 had a high O(6)MGMT activity. Two out of 3 cases with a low O(6)MGMT activity in each primary lesion did not show any evidence of metastasis or local recurrence. The evaluation of O(6)MGMT activity in melanoma may, therefore, be useful to determine the characteristics of tumor in each melanoma case. In addition, the present study implies the possibility of selective cancer chemotherapy for melanoma in the near future.