title: Macrophage migration inhibitory factor protein and mRNA expression in cutaneous melanocytic tumours.
abstract: 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.
authors.affiliation: Sezione di Anatomia Patologica, Dipartimento di Patologia Umana e Oncologia, Università di Siena, 53100 Siena, Italy. miracco@unisi.it
authors.forename: Clelia
authors.initials: C
authors.lastname: Miracco
authors.forename: Maria Caterina
authors.initials: MC
authors.lastname: De Nisi
authors.forename: Felice
authors.initials: F
authors.lastname: Arcuri
authors.forename: Elena
authors.initials: E
authors.lastname: Cosci
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Pacenti
authors.forename: Marzia
authors.initials: M
authors.lastname: Toscano
authors.forename: Anna Vittoria
authors.initials: AV
authors.lastname: Lalinga
authors.forename: Maurizio
authors.initials: M
authors.lastname: Biagioli
authors.forename: Pietro
authors.initials: P
authors.lastname: Rubegni
authors.forename: Rosella
authors.initials: R
authors.lastname: Vatti
authors.forename: Emilia
authors.initials: E
authors.lastname: Maellaro
authors.forename: Barbara
authors.initials: B
authors.lastname: Del Bello
authors.forename: Daniela
authors.initials: D
authors.lastname: Massi
authors.forename: Pietro
authors.initials: P
authors.lastname: Luzi
authors.forename: Piero
authors.initials: P
authors.lastname: Tosi
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D009362:Neoplasm Metastasis; D009508:Nevus, Pigmented / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D008263:Macrophage Migration-Inhibitory Factors; D012333:RNA, Messenger