Detection of certain molecular markers such as deletion of 1p and 19q chromosomal arms, hypermethylation of MGMT promoter, and characteristic PTEN exon mutations may help differentiate subtypes which are more prone to extracranial metastases.
Intratumor heterogeneity for expression of P16INK4a and MGMT may reflect intratumor heterogeneity for methylation patterns and thereby in general explain the moderate sensitivity of our marker panel for detection of metastases.
Analysis of MGMT promoter methylation comparing primaries and different metastases over the clinical course revealed no statistical difference (P=0.49).
Features of the primary neoplasm that predicted resolution of the metastases were absence of tumor budding (P = 0.04), absence of a diffusely infiltrative tumor margin (P = 0.02), and loss of expression of the DNA repair gene O6-methylguanine-DNA methyltransferase (P = 0.08).
In a retrospective study, O(6)-methylguanine-DNA-methyltransferase (MGMT) expression was analysed by immunohistochemistry using monoclonal human anti-MGMT antibody in melanoma metastases in patients receiving dacarbazine (DTIC) as single-drug therapy or as part of combination chemotherapy with DTIC-vindesine or DTIC-vindesine-cisplatin.