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Macrophage migration inhibitory factor (MIF) is a widely expressed cytokine involved in various biological processes. Although MIF's functions in cancer have not been completely elucidated, its expression has usually been correlated with tumour progression and aggressiveness, and it is currently discussed as a new promising target for novel therapies. Recent studies seem to confirm its active role in melanoma pathobiology; however, its expression has not yet been extensively studied in melanocytic tumours. We evaluated MIF protein expression in 126 skin lesions, including benign and atypical nevi, melanoma and melanoma metastases. In 55 cases, we also assessed MIF mRNA expression by real-time RT-PCR. Benign nevi were subdivided into nevocytic and Spitz/blue types; and melanomas into the radial, and vertical growth phase. A strong cytoplasmic MIF positivity was found in most samples, although it was more heterogeneous in malignant tumours; MIF nuclear expression characterized Spitz/blue nevi, atypical nevi, melanomas and metastases. All samples expressed MIF mRNA but it was significantly lower in benign nevi vs atypical nevi, melanomas and metastases (p=0.001; p<0.0001; p=0.002, respectively). Our study shows a widespread distribution of MIF among melanocytic tumours. Whereas we observed a trend towards higher expression levels of mRNA in atypical and malignant tumours, MIF protein was highly expressed in all lesions, although limited to the cytoplasm in most benign nevi. These observations suggest differences in MIF protein storage, subcellular location and properties in most benign nevi vs atypical and malignant tumours that should be confirmed by further investigation and correlation with clinical outcome.

Aberrations of genes/proteins regulating cell cycle and growth, increased proliferation and telomerase activity (TA) are documentable in glioblastoma multiforme. TA is more frequently detectable in secondary glioblastoma, which is also characterized by p53 mutation/overexpression. Discordant telomere (Te) length values have been reported in glioblastomas with and without TA. In 31 glioblastomas, in which pre-existing astrocytoma was not documented, we compared cases with and without TA for the expression of p53, EGFR, c-Myc, MIB-1 and Topoisomerase IIalpha; p53 mutations were also investigated by SSCP-PCR. Correlations were made with Te parameters [TePs: number (TeNo), length and area] as evaluated by image analysis in interphase nuclei of fluorescence in situ hybridization (FISH)-processed sections. We found no differences in the expression of the proteins evaluated and in TePs, except Te/nuclear area %, which was significantly lower in TA+ cases (p=0.02). TePs were, instead, inversely correlated with TA (p=0.0001). TA was positively correlated with MIB1 staining index in the TA+ cases (p=0.033), which also showed a positive correlation between TeNo and EGFR expression (p=0.042), and a trend towards a negative correlation between TeNo and p53 expression (p=0.05). Tumors overexpressing EGFR had a significantly shorter lifetime (p=0.0001). TeNo seems to be inversely correlated to tumor proliferation and lifetime in glioblastoma multiforme.