Weinlich G, Topar G, Eisendle K, Fritsch P O, Zelger B
Clinical Department of Dermatology and Venerology, Innsbruck Medical University, Innsbruck, Austria.
J Eur Acad Dermatol Venereol. 2007 May;21(5):669-77. doi: 10.1111/j.1468-3083.2006.02051.x.
Metallothioneins (MT) are ubiquitous, intracellular small proteins with high affinity for heavy metal ions. Immunohistochemical MT overexpression in paraffin-embedded tissues of patients with primary melanoma is associated with poor prognosis. While sentinel lymph node (SLN) biopsy is an established surgical technique for high-risk melanoma patients with predictive value for progression, the benefit of this procedure for the individual patient's overall survival remains unclear.
We examined the role of MT overexpression in comparison with SLN biopsy in melanoma patients as a prognostic marker for progression and survival. One hundred and fifty-eight (158) patients underwent SLN biopsy due to high-risk melanoma. Primary melanoma specimens were investigated by using a monoclonal antibody against MT on routinely fixed, paraffin-embedded tissues. The patients were followed up (median 37 months); the data of disease free survival and overall survival were calculated with a broad panel of statistical analyses.
Twenty-eight (18%) out of 158 recruited melanoma patients developed metastases, 17 (11%) patients died due to widespread disease. Kaplan-Meier curves gave significant disadvantages for the MT-positive as well as the SLN-positive group for progression and survival. In the Fisher's exact test and Pearson's chi(2)-test MT overexpression was highly significant for progression, whereas SLN biopsy failed significance. In univariate as well as multivariate Cox regression analysis MT overexpression proved an excellent marker for progression (P=0.007 and P=0.009), although the P-values for survival were not significant. In contrast, while in the univariate analysis SLN biopsy did not show significant results for progression it did for survival, and in the multivariate analysis reached a P-value < 0.05 for both measured endpoints.
Results corroborate the validity of MT overexpression in primary melanoma as a useful prognostic marker in melanoma patients. Accuracy is comparable and to some degree supplementary to the results of SLN biopsy.
金属硫蛋白（MT）是一种普遍存在的细胞内小蛋白，对重金属离子具有高亲和力。原发性黑色素瘤患者石蜡包埋组织中MT免疫组化过表达与预后不良相关。虽然前哨淋巴结（SLN）活检是一种成熟的手术技术，对高危黑色素瘤患者的病情进展具有预测价值，但该手术对个体患者总生存期的益处仍不明确。
我们研究了MT过表达与SLN活检相比，在黑色素瘤患者中作为病情进展和生存预后标志物的作用。158例高危黑色素瘤患者接受了SLN活检。原发性黑色素瘤标本采用抗MT单克隆抗体，在常规固定、石蜡包埋的组织上进行检测。对患者进行随访（中位时间37个月）；通过一系列统计分析计算无病生存期和总生存期数据。
158例招募的黑色素瘤患者中，28例（18%）发生转移，17例（11%）患者因疾病广泛播散死亡。Kaplan-Meier曲线显示，MT阳性组和SLN阳性组在病情进展和生存方面均有显著劣势。在Fisher精确检验和Pearson卡方检验中，MT过表达对病情进展具有高度显著性，而SLN活检无显著性。在单变量和多变量Cox回归分析中，MT过表达被证明是病情进展的优秀标志物（P = 0.007和P = 0.009），尽管生存的P值不显著。相比之下，虽然在单变量分析中SLN活检对病情进展未显示显著结果，但对生存有显著结果，并且在多变量分析中，两个测量终点的P值均< 0.05。
结果证实原发性黑色素瘤中MT过表达作为黑色素瘤患者有用的预后标志物的有效性。准确性与SLN活检结果相当，且在一定程度上具有互补性。
