Rangel Javier, Nosrati Mehdi, Torabian Sima, Shaikh Ladan, Leong Stanley P L, Haqq Chris, Miller James R, Sagebiel Richard W, Kashani-Sabet Mohammed
Auerback Melanoma Research Laboratory, Cutaneous Oncology Program, University of California-San Francisco Comprehensive Cancer Center, San Francisco, California 94115, USA.
Cancer. 2008 Jan 1;112(1):144-50. doi: 10.1002/cncr.23147.
Osteopontin has been suggested as a marker of disease progression in patients with melanoma because of its overexpression in recent microarray analyses. However, its prognostic role in melanoma has not been fully defined.
Osteopontin expression status was examined using immunohistochemical analysis of a tissue microarray that contained primary cutaneous melanomas from 345 patients. The correlation between osteopontin expression and several histologic markers for melanoma was assessed by using the Chi-square test and the Le directional test. The impact of osteopontin expression on recurrence-free survival (RFS) and disease-specific survival (DSS) of patients with melanoma was examined using Cox regression and Kaplan-Meier analyses. The impact of increasing osteopontin expression on sentinel lymph node (SLN) metastasis was assessed using logistic regression analysis.
High osteopontin expression was associated with increased tumor thickness (P = .037), Clark level (P = .035), and mitotic index (P = .046). Kaplan-Meier analysis demonstrated an association between osteopontin expression and reduced RFS (P < .03) and DSS (P = .05). Multivariate Cox regression analysis demonstrated that high osteopontin immunostaining had an independent impact on the DSS of this melanoma cohort (P = .049). In addition, osteopontin expression was significantly predictive of SLN metastasis (P = .009) and SLN burden, as assessed by the mean number of SLN metastases (P = .0025). Multivariate logistic regression analysis demonstrated an independent role for osteopontin expression in predicting SLN status (P = .0062).
The current results validated the role of osteopontin as an independent prognostic marker for melanoma and provided new evidence for its predictive role in melanoma lymph node metastasis.
骨桥蛋白在最近的微阵列分析中过度表达，因此被认为是黑色素瘤患者疾病进展的标志物。然而，其在黑色素瘤中的预后作用尚未完全明确。
使用免疫组织化学分析法检测包含345例原发性皮肤黑色素瘤的组织微阵列的骨桥蛋白表达状态。采用卡方检验和勒定向检验评估骨桥蛋白表达与黑色素瘤几种组织学标志物之间的相关性。使用Cox回归和Kaplan-Meier分析检查骨桥蛋白表达对黑色素瘤患者无复发生存期（RFS）和疾病特异性生存期（DSS）的影响。使用逻辑回归分析评估骨桥蛋白表达增加对前哨淋巴结（SLN）转移的影响。
骨桥蛋白高表达与肿瘤厚度增加（P = 0.037）、克拉克分级（P = 0.035）和有丝分裂指数增加（P = 0.046）相关。Kaplan-Meier分析表明骨桥蛋白表达与RFS降低（P < 0.03）和DSS降低（P = 0.05）相关。多变量Cox回归分析表明，骨桥蛋白免疫染色高对该黑色素瘤队列的DSS有独立影响（P = 0.049）。此外，骨桥蛋白表达可显著预测SLN转移（P = 0.009）和SLN负荷，以前哨淋巴结转移的平均数量评估（P = 0.0025）。多变量逻辑回归分析表明骨桥蛋白表达在预测SLN状态方面具有独立作用（P = 0.0062）。
当前结果证实了骨桥蛋白作为黑色素瘤独立预后标志物的作用，并为其在黑色素瘤淋巴结转移中的预测作用提供了新证据。
