title: Maspin expression and melanoma progression: a matter of sub-cellular localization.
abstract: Maspin, a member of the serpin family of protease inhibitors, is involved in key processes of cancer progression. Its biological activity seems to be cancer and compartment specific, with the protein acting either as a suppressor or as a tumor promoter in different cancer types. Characterization of maspin expression and its sub-cellular localization in melanoma is missing, hence, we aim to investigate its possible association with melanoma prognostic factors and disease progression. Nuclear and cytoplasmic maspin expression were evaluated on 60 nevi, 152 primary lesions, and 106 melanoma metastases using tissue microarrays and immunohistochemistry. The association between maspin immunoreactivity and patient's clinic-pathological features was evaluated. Multivariate logistic models and survival analyses were performed for maspin expression in primary melanomas. Nuclear maspin was detected in 8% nevi, 49% primary melanomas, and 28% metastases, whereas cytoplasmic maspin in 12% nevi, 18% primary lesions, and 9% metastases. In univariate analysis, nuclear maspin expression in primary melanomas was significantly associated with melanoma prognostic factors (nodular histotype, tumor thickness, mitotic rate, and ulceration) and disease stage, whereas cytoplasmic maspin was observed at higher frequency in thin superficial spreading melanomas, without mitosis. In multivariate analysis, nuclear maspin remained significantly associated with risk of developing a tumor prone to disease progression and, accordingly, with significantly shorter disease-free and overall survival. In this study, maspin was expressed at highest frequency in primary lesions and when expressed in the nuclei, was significantly associated with poor prognostic markers, melanoma recurrence, and worse survival. The present study suggests a tumor-suppressive effect of cytoplasmic maspin and a tumor-promoting effect of nuclear maspin, which open the discussion on its potential use in cancer therapy.
authors.affiliation: Medical Oncology of Melanoma Unit, Division of Medical Oncology, European Institute of Oncology, Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Martinoli
authors.affiliation: Division of Statistics and Epidemiology, European Institute of Oncology, Milan, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Gandini
authors.affiliation: Molecular Medicine for Care Program, European Institute of Oncology, Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Luise
authors.affiliation: Molecular Medicine for Care Program, European Institute of Oncology, Milan, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Mazzarol
authors.affiliation: Molecular Medicine for Care Program, European Institute of Oncology, Milan, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Confalonieri
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology, Milan, Italy.
authors.forename: Pier
authors.initials: P
authors.lastname: Giuseppe Pelicci
authors.affiliation: Division of Melanoma and Soft Tissue Sarcomas, European Institute of Oncology, Milan, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Testori
authors.affiliation: Medical Oncology of Melanoma Unit, Division of Medical Oncology, European Institute of Oncology, Milan, Italy.
authors.forename: Pier Francesco
authors.initials: PF
authors.lastname: Ferrucci
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D018450:Disease Progression; D006801:Humans; D053208:Kaplan-Meier Estimate; D008545:Melanoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D009362:Neoplasm Metastasis / Q000473:pathology; D016016:Proportional Hazards Models; D015843:Serpins / Q000032:analysis / Q000096:biosynthesis*; D012878:Skin Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; C085344:SERPIN-B5; D015843:Serpins