INCREASED THYMIDYLATE SYNTHASE GENE-EXPRESSION IN METASTATIC MELANOMA

Thymidylate synthase (TS) provides the only de novo source of thymidyl ate for DNA synthesis and is a key target for cancer chemotherapeutic agents. We investigated the TS gene expression by semiquantitative rev erse-transcriptase polymerase chain reaction in metastatic melanoma an d compared the results with those from control tissues. The relative T S/beta-actin level ratios were 0.5, 0.9, 0.3, 0.4, and 0.5 (mean 0.5) in skin, lymph node, thyroid, muscle, and spleen, respectively. In met astatic melanoma samples, the ratios varied from 0.9 to 2.7 (mean 2.0) . The differences of expression levels between these two groups of sam ples were statistically highly significant (p=0.0000713). A similar st atistical significance (p=0.0002) was observed between patients achiev ing a complete response and patients who had progressive disease despi te immunochemotherapy. There was no clear relationship between a high TS/beta-actin ratio and the S phase fraction, as all melanomas had a h igh S phase fraction.