Naffouje Samer, Naffouje Rand, Bhagwandin Shanel, Salti George I
Departments of aGeneral Surgery bSurgical Oncology, University of Illinois at Chicago Medical Center cDepartment of Medicine, Weiss Memorial Hospital, Chicago, Illinois, USA.
Melanoma Res. 2015 Dec;25(6):496-502. doi: 10.1097/CMR.0000000000000195.
Microphthalmia transcription factor (Mitf) is involved in melanocyte development and differentiation. We previously reported that Mitf expression, as detected by immunohistochemical analysis, is an independent prognostic marker in patients with intermediate-thickness melanoma. However, the clinical significance of Mitf expression in melanoma is not well delineated. In this prospective study, we attempted to demonstrate the correlation between Mitf expression in primary melanoma and the sentinel lymph node status and prognosis. We prospectively examined primary cutaneous melanomas from 94 patients undergoing nodal staging by sentinel lymph node biopsy. We quantified the percentage of tumor cells whose nuclei stained with the Mitf antibody visually. Survival curves were generated using the Kaplan-Meier method. The correlation between Mitf expression and nodal status was evaluated using the Mann-Whitney U-test. Here we demonstrate that Mitf expression is directly correlated with both disease-free survival (DFS) and overall survival (OS) over a median follow-up of 28.5 months. The mean DFS and OS in the eight patients whose melanomas did not stain positive for Mitf were 15.75±3.36 months (median, 12 months) and 38.17±5.18 months (median, 29 months), respectively. These results are significantly lower than those for patients who showed evidence of Mitf expression, in whom the mean DFS and OS were 66.1±4.03 months (median, not reached, P=0.0001) and 66.75±38.17 months (median, not reached, P=0.0001), respectively. The mean DFS and OS with greater than 25% (67 patients) of the melanoma cells staining positive for Mitf expression were 78.37±2.78 and 82.38±1.6 months, respectively, compared with 26.37±3.2 months (P=0.0001) and 44.53±4.5 months (P=0.0001), respectively, with up to 25% (27 patients) of cells stained positive for Mitf expression. In addition, there was a significant relationship between Mitf expression and nodal status, as evaluated by sentinel node biopsy. For example, none of the melanomas with greater than 50% Mitf expression had a positive sentinel node biopsy. Our study shows that expression of the molecular marker Mitf in primary cutaneous melanomas is a useful tool in assessing lymph node status. Mitf immunostaining in the primary tumor serves as a reliable predictor of occult lymph node metastases, as well as a favorable prognosticator of DFS and OS in melanoma patients.
小眼畸形转录因子（Mitf）参与黑素细胞的发育和分化。我们之前报道，通过免疫组织化学分析检测到的Mitf表达是中厚型黑色素瘤患者的一个独立预后标志物。然而，Mitf表达在黑色素瘤中的临床意义尚未完全阐明。在这项前瞻性研究中，我们试图证明原发性黑色素瘤中Mitf表达与前哨淋巴结状态及预后之间的相关性。我们前瞻性地检查了94例接受前哨淋巴结活检进行淋巴结分期的患者的原发性皮肤黑色素瘤。我们通过视觉量化用Mitf抗体染色的肿瘤细胞核的百分比。使用Kaplan-Meier方法生成生存曲线。使用Mann-Whitney U检验评估Mitf表达与淋巴结状态之间的相关性。在此我们证明，在中位随访28.5个月期间，Mitf表达与无病生存期（DFS）和总生存期（OS）均直接相关。Mitf染色未呈阳性的8例患者的平均DFS和OS分别为15.75±3.36个月（中位数为12个月）和38.17±5.18个月（中位数为29个月）。这些结果显著低于有Mitf表达证据的患者，后者的平均DFS和OS分别为66.1±4.03个月（中位数未达到，P = 0.0001）和66.75±38.17个月（中位数未达到，P = 0.0001）。Mitf表达阳性的黑色素瘤细胞超过25%（67例患者）的平均DFS和OS分别为78.37±2.78个月和82.38±1.6个月，而Mitf表达阳性的细胞高达25%（27例患者）时，平均DFS和OS分别为26.37±3.2个月（P = 0.0001）和44.53±4.5个月（P = 0.0001）。此外，通过前哨淋巴结活检评估，Mitf表达与淋巴结状态之间存在显著关系。例如，Mitf表达大于50%的黑色素瘤中，没有前哨淋巴结活检呈阳性的情况。我们的研究表明，原发性皮肤黑色素瘤中分子标志物Mitf的表达是评估淋巴结状态的有用工具。原发性肿瘤中的Mitf免疫染色可作为隐匿性淋巴结转移的可靠预测指标，以及黑色素瘤患者DFS和OS的良好预后指标。
