NM23 NUCLEOSIDE DIPHOSPHATE (NDP) KINASE EXPRESSION IN HUMAN-MALIGNANT MELANOMAS - SIGNIFICANCE AND IMPLICATIONS IN TUMOR BIOLOGY/

The nm23/NDP kinase gene located on chromosome 17q has been proposed a s metastasis suppressor gene in a variety of tumor types. Nm23 was ini tially isolated from the highly metastatic murine K-1735 melanoma cell line and levels of nm23 have been found to correlate inversely with m etastatic potential in some tumors, but not in others. In the present immunocytochemical study, we investigated nm23 protein expression in 3 0 primary cutaneous malignant melanomas (CMs) and 10 metastases of mal ignant cutaneous melanomas (MMCMs) which had already metastasized to a distant site. We employed a sensitive, phosphatase conjugated biotin- streptavidin cytochemical technique using the anti-nm23 affinity purif ied rabbit anti-human polyclonal antibody on formalin fixed paraffin e mbedded tissue sections of the malignant melanomas. We found nm23 expr ession in 24 out of 30 CMs with between 10% and 50% of the melanoma ce lls exhibiting immunoreactivity with the employed antibody. None of th e ten MCMMs expressed nm23. As we described in a previous article (48) , malignant melanoma is characterized by a high degree of cellular imm unophenotype heterogeneity. in further support of this observation, we observed a diverse level of nm23 staining intensity in the cell subpo pulations which comprises the tumor microenvironment. Nm23/NDP kinase has a diverse array of biological functions including roles in signal transduction and microtubule assembly. In our opinion, the many roles of nm23/NDP kinase are mainly involved in cell division and this may b e the underlying reason that levels of this protein do not truly corre late with metastatic potential. Therefore, nm23 protein levels may cor relate well with proliferative rate and degree of tumor specific dedif ferentiation which are important parameters to be established in the e arly diagnosis, monitoring of neoplasma progression and efficacy of em ployed clinical trials, and the determination of prognosis of every ne oplastic disease.