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.

Association between the clinical and histopathological classifications of actinic keratosis and the efficacy of topical imiquimod treatment.

We investigated the association between the clinical and histopathological classifications of actinic keratosis (AK) and the efficacy of topical imiquimod treatment. Forty patients (55 lesions) with AK were treated with topical 5% imiquimod and the efficacy of imiquimod for AK was evaluated based on the clinical/histopathological changes. The complete remission (CR) rates in patients with the different clinical classifications of AK were 85.4% (erythematous type) and 46.2% (hyperkeratotic type). The CR rates in the different histopathological classifications of AK were 80% (hypertrophic type), 81.8% (atrophic type) and 42.9% (bowenoid type). The results revealed that determining the clinical and histopathological type of AK was important for selecting a therapeutic method. The topical imiquimod treatment could be expected to be more effective for AK clinically classified as the erythematous type, or histopathologically classified as the atrophic or hypertrophic type. However, it would be expected to be less effective for the treatment of AK clinically classified as the hyperkeratotic type or histopathologically classified as the bowenoid type. Our observations suggest that we can predict the efficacy of topical imiquimod therapy in AK by determining its clinical and histopathological type.

5-Aminolevulinic acid-mediated photodynamic therapy to superficial malignant skin tumors using Super Lizer.

Photodynamic therapy (PDT) using topically applied 5-aminolevulinic acid (ALA) has become a generally accepted treatment modality for superficial malignant skin tumors. However, the costly excimer-dye laser, diode laser and light-emitting diode (LED) frequently used to administrate PDT are impractical to use in most dermatology clinics. This study evaluated the effectiveness of ALA-mediated PDT using a Super Lizer (Tokyo Iken, Tokyo, Japan) equipped with band-pass filters in 38 patients with superficial malignant skin tumors (33 cases of actinic keratosis and five cases of Bowen's disease). Twenty-one cases (18 cases of actinic keratosis and three cases of Bowen's disease) were successfully treated, and the other 17 cases (15 cases of actinic keratosis and two cases of Bowen's disease) showed partial remission after single or repeated administration of PDT. PDT repeated three times at weekly intervals was more effective against actinic keratosis than randomly repeated procedures. The Super Lizer is easy to handle and move, and is less expensive than other known machinery and is useful for PDT in dermatology, especially under the protocol of three times at weekly intervals for the treatment of actinic keratosis.