Babapoor Sankhiros, Horwich Michael, Wu Rong, Levinson Shauna, Gandhi Manoj, Makkar Hanspaul, Kristjansson Arni, Chang Mary, Dadras Soheil S
Department of Genetics and Genomic Sciences, University of Connecticut Health Center, Farmington, CT, USA.
Department of Dermatology, University of Connecticut Health Center, Farmington, CT, USA.
Mod Pathol. 2016 May;29(5):461-75. doi: 10.1038/modpathol.2016.44. Epub 2016 Feb 26.
Some melanocytic tumors can be histologically ambiguous causing diagnostic difficulty, which could lead to overtreatment of benign lesions with an unwarranted psychological distress or undertreatment of malignant cancers. Previously, we demonstrated that significantly decreased miR-211 expression in melanomas compared with melanocytic nevi could accurately discriminate malignant from benign tumors. Herein we show microRNA in situ hybridization for fluorescent detection of miR-211, suitable for paraffin-embedded tissues in 109 primary melanocytic tumors. miR-211 expression was significantly lower in melanomas vs nevi (P<0.0001), and receiver operating characteristic curve (area under the curve=0.862) accurately discriminated melanomas from nevi with 90% sensitivity and 86.2% specificity. Qualitatively, all dysplastic nevi expressed miR-211 at high (86%) and low (14%) levels, independent of the degree of nuclear atypia. All 35 melanocytic tumors with Spitz morphology expressed miR-211 independent of morphological classification, where clinical follow-up of these patients showed no recurrence at the site or metastasis in mean and median of 3 (ranging 2-5) years. Moreover, a decision tree learning analysis selected age and miR-211 miRNA in situ hybridization as the predictive variables for benign or malignant outcome in 88 patients correctly classified 92% (81 out of 88) of cases as proven by receiver operating characteristic curve (area under the curve=0.9029). These results support miR-211 as a leading miRNA candidate for melanoma diagnosis and miRNA in situ hybridization as a uniquely uncomplicated ancillary test.
一些黑素细胞肿瘤在组织学上可能存在不明确性，导致诊断困难，这可能会导致对良性病变进行过度治疗，给患者带来不必要的心理困扰，或者对恶性肿瘤治疗不足。此前，我们证明，与黑素细胞痣相比，黑色素瘤中miR-211表达显著降低，这可以准确地区分良性和恶性肿瘤。在此，我们展示了用于荧光检测miR-211的微RNA原位杂交技术，适用于109例原发性黑素细胞肿瘤的石蜡包埋组织。黑色素瘤中的miR-211表达明显低于痣（P<0.0001），并且受试者工作特征曲线（曲线下面积=0.862）以90%的灵敏度和86.2%的特异性准确地区分了黑色素瘤和痣。定性地说，所有发育异常痣均高（86%）低（14%）水平表达miR-211，与核异型程度无关。所有35例具有Spitz形态的黑素细胞肿瘤均表达miR-211，与形态学分类无关，这些患者的临床随访显示，在平均3年（范围2-5年）的时间里，该部位无复发或转移。此外，决策树学习分析选择年龄和miR-211微RNA原位杂交作为88例患者良性或恶性结果的预测变量，经受试者工作特征曲线验证（曲线下面积=0.9029），正确分类了92%（88例中的81例）的病例。这些结果支持miR-211作为黑色素瘤诊断的主要微RNA候选物，以及微RNA原位杂交作为一种独特的、简单的辅助检测方法。
