Medical Oncology of Melanoma Unit, Division of Medical Oncology, European Institute of Oncology, Milan, Italy.
Division of Statistics and Epidemiology, European Institute of Oncology, Milan, Italy.
Mod Pathol. 2014 Mar;27(3):412-9. doi: 10.1038/modpathol.2013.157. Epub 2013 Sep 13.
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.
Maspin 是丝氨酸蛋白酶抑制剂家族的一员，参与了癌症进展的关键过程。它的生物学活性似乎具有癌症和细胞区室特异性，该蛋白在不同的癌症类型中既可以作为抑制物，也可以作为肿瘤促进物发挥作用。黑色素瘤中 maspin 的表达及其亚细胞定位特征尚未得到描述，因此，我们旨在研究其与黑色素瘤预后因素和疾病进展的可能相关性。使用组织微阵列和免疫组织化学技术，对 60 个痣、152 个原发性病变和 106 个黑色素瘤转移灶进行了核浆 maspin 表达的评估。评估了 maspin 免疫反应性与患者临床病理特征之间的关联。对原发性黑色素瘤中 maspin 表达进行了多变量逻辑模型和生存分析。在 8%的痣、49%的原发性黑色素瘤和 28%的转移灶中检测到核 maspin，而在 12%的痣、18%的原发性病变和 9%的转移灶中检测到细胞质 maspin。在单因素分析中，原发性黑色素瘤中的核 maspin 表达与黑色素瘤的预后因素（结节型组织学类型、肿瘤厚度、有丝分裂率和溃疡）和疾病分期显著相关，而细胞质 maspin 则在无有丝分裂的薄型浅表扩散性黑色素瘤中更为常见。在多变量分析中，核 maspin 仍然与发展为易于发生疾病进展的肿瘤的风险显著相关，因此与无病生存期和总生存期显著缩短相关。在这项研究中，mpsin 在原发性病变中表达频率最高，而在细胞核中表达时，与不良预后标志物、黑色素瘤复发和较差的生存显著相关。本研究表明细胞质 maspin 具有肿瘤抑制作用，核 maspin 具有肿瘤促进作用，这为其在癌症治疗中的潜在应用开辟了讨论空间。
