Staibano Stefania, Pepe Stefano, Lo Muzio Lorenzo, Somma Pasquale, Mascolo Massimo, Argenziano Giuseppe, Scalvenzi Massimiliano, Salvatore Gaetano, Fabbrocini Gabriella, Molea Guido, Bianco Angelo Raffaele, Carlomagno Chiara, De Rosa Gaetano
Pathology Section, Department of Biomorphological and Functional Sciences, University Federico II of Naples, 80127 Naples, Italy.
Hum Pathol. 2005 Jul;36(7):724-31. doi: 10.1016/j.humpath.2005.04.017.
The family of the poly(adenosine diphosphate-ribose) polymerase (PARP) proteins is directly involved in genomic stability, DNA repair, and apoptosis by DNA damage. In this study, we evaluated the role of PARP-1 in melanoma and its prognostic importance. We studied by immunohistochemistry and Western blot analysis PARP-1 expression in a selected series of 80 primary melanoma of the head and neck region. The results were correlated with tumor thickness and patient's outcome. A follow-up of at least 3 years was available. Fifteen cases of benign melanocytic nevi were used as controls. Normal melanocytes showed only scattered, focal nuclear positivity and were considered as negative for PARP-1 expression by immunohistochemistry (score, 0). Thirty cases of melanoma (37.5%) showed nuclear expression of PARP-1 in both radial and vertical growth phases. Western blot analysis showed the presence of a high signal for full-length PARP-1 only in the cases with high immunohistochemical (nuclear) expression of protein (score, ++/+++) in both radial and vertical growth phase. A significant correlation was present between PARP-1 expression in vertical growth phase and the thickness of tumor lesion (P = .014); all but one tumor measuring less than 0.75 mm showed no or low PARP-1 expression. No correlation was found between PARP-1 expression in radial growth phase and tumor thickness (P = .38, data not shown). These data suggest that PARP-1 overexpression is a potential novel molecular marker of aggressive cutaneous malignant melanoma and a direct correlation between PARP-1-mediated inhibition of the apoptosis and biologic behavior of cutaneous malignant melanoma.
聚（腺苷二磷酸 - 核糖）聚合酶（PARP）蛋白家族直接参与基因组稳定性、DNA修复以及由DNA损伤引发的细胞凋亡过程。在本研究中，我们评估了PARP - 1在黑色素瘤中的作用及其预后重要性。我们通过免疫组织化学和蛋白质印迹分析研究了80例头颈部原发性黑色素瘤中PARP - 1的表达情况。结果与肿瘤厚度和患者预后相关。所有患者均有至少3年的随访数据。15例良性黑素细胞痣用作对照。正常黑素细胞仅显示散在的、局灶性核阳性，免疫组织化学检测PARP - 1表达被视为阴性（评分，0）。30例黑色素瘤（37.5%）在放射状和垂直生长期均显示PARP - 1的核表达。蛋白质印迹分析表明，仅在放射状和垂直生长期蛋白质免疫组织化学（核）高表达（评分，++/+++）的病例中存在全长PARP - 1的高信号。垂直生长期PARP - 1表达与肿瘤病变厚度之间存在显著相关性（P = .014）；除1例肿瘤外，所有直径小于0.75 mm的肿瘤均未显示或低表达PARP - 1。放射状生长期PARP - 1表达与肿瘤厚度之间未发现相关性（P = .38，数据未显示）。这些数据表明，PARP - 1过表达是侵袭性皮肤恶性黑色素瘤潜在的新型分子标志物，且PARP - 1介导的细胞凋亡抑制与皮肤恶性黑色素瘤的生物学行为之间存在直接相关性。
