Department of Pathology, 12 de Octubre University Hospital, Madrid, Spain.
Mod Pathol. 2010 Sep;23(9):1215-24. doi: 10.1038/modpathol.2010.102. Epub 2010 Jun 11.
Several isolated markers have been proposed to aid in differential diagnostic of difficult melanocytic lesions, albeit none has been shown to be definitive in differentiating Spitz nevus from melanoma. This study proposes a wide panel of 22 markers having important functions in different biological functions (cell cycle, apoptosis, DNA repair proteins and membranous receptors) to provide a combination of proteins associated with either benign or malignant phenotype. Using tissue microarrays, we compared protein expression profiles in 28 typical Spitz nevi and 62 primary vertical growth phase non-spitzoid melanomas. Most of the significant differences were linked to cell-cycle deregulation such as overexpression of cyclin D1 and p21 in Spitz nevi compared with non-spitzoid melanomas (74 vs 16% and 91 vs 27%, respectively) and mitotic rate including Ki-67, highly expressed in deep areas of non-spitzoid melanomas (37%), whereas it is not expressed in Spitz nevi (0%), topoisomerase IIalpha (79% in non-spitzoid melanomas vs 15% in Spitz nevi) and nuclear survivin (69% in melanomas vs 0% in Spitz nevi). A combination of biological markers differentially expressed in Spitz nevi from non-spitzoid melanomas is defined, thus providing a potential tool for histopathological differential diagnostic between Spitz nevus and melanoma. Nevertheless, more studies including atypical Spitz nevi and spitzoid melanomas are necessary to further establish a reliable panel to differentiate among difficult cases.
已经提出了一些孤立的标记物来辅助鉴别诊断具有挑战性的黑色素细胞病变,但没有一种标记物被证明可以明确地区分 Spitz 痣与黑色素瘤。本研究提出了一个广泛的 22 个标记物面板,这些标记物具有重要的生物学功能(细胞周期、凋亡、DNA 修复蛋白和膜受体),提供了与良性或恶性表型相关的蛋白质组合。使用组织微阵列,我们比较了 28 例典型 Spitz 痣和 62 例原发性垂直生长阶段非 Spitz 样黑色素瘤的蛋白表达谱。大多数显著差异与细胞周期失调有关,例如与非 Spitz 样黑色素瘤相比,Spitz 痣中 cyclin D1 和 p21 的过度表达(分别为 74%对 16%和 91%对 27%)和有丝分裂率包括 Ki-67,在非 Spitz 样黑色素瘤的深部区域高度表达(37%),而在 Spitz 痣中不表达(0%),拓扑异构酶 IIalpha(非 Spitz 样黑色素瘤中为 79%,Spitz 痣中为 15%)和核生存素(黑色素瘤中为 69%,Spitz 痣中为 0%)。定义了在 Spitz 痣与非 Spitz 样黑色素瘤之间差异表达的生物标记物组合,从而为 Spitz 痣与黑色素瘤的组织病理学鉴别诊断提供了潜在的工具。然而,需要更多包括非典型 Spitz 痣和 Spitz 样黑色素瘤的研究来进一步建立一个可靠的面板来区分困难病例。