Abstract：
Long noncoding RNAs (lncRNAs) participate in transcriptional, epigenetic, and post-transcriptional regulation of gene expression and may influence carcinogenesis. MALAT1 is a lncRNA that is expressed in endocrine and many other neoplasms and it has been shown to have oncogenic and/or tumor suppressor effects in tumor development. Olfactory neuroblastomas arise in the nasal cavity while sympathetic neuroblastomas are present mainly in the adrenal and periadrenal regions. These neoplasms have overlapping histopathological features. Rare cases of sympathetic neuroblastomas metastatic to the nasal cavity have been reported. PHOX2B has been shown to be relatively specific for sympathetic neuroblastomas, but only a limited number of cases of olfactory neuroblastomas have been examined for PHOX2B expression. This study aimed to explore the potential utilization of MALAT1 and PHOX2B in distinguishing these two entities. Tissue microarrays (TMA) were created for olfactory neuroblastomas (n = 26) and sympathetic neuroblastomas (n = 52). MALAT1 lncRNA expression was assessed by in situ hybridization using RNAScope technology. TMA slides were scanned by Vectra multispectral imaging system and image analysis and quantification were performed with inForm software. PHOX2B expression was analyzed by immunohistochemistry. MALAT1 showed predominantly nuclear expression in both tumor types and MALAT1 expression was 2-fold higher in olfactory neuroblastomas compared to sympathetic neuroblastomas (p < 0.0001). PHOX2B showed nuclear staining in most sympathetic neuroblastomas (51/52, 98 %) while only 1 olfactory neuroblastoma (3.8 %) was focally positive for this marker. These findings suggest immunostaining of PHOX2B could be an excellent marker in distinguishing between these two tumor types.
摘要：
长链非编码RNA（lncRNAs）参与转录，表观遗传,和基因表达的转录后调控，并可能影响致癌作用。MALAT1是一种lncRNA，在内分泌和许多其他肿瘤中表达，并已显示在肿瘤发展中具有致癌和/或肿瘤抑制作用。嗅觉神经母细胞瘤出现在鼻腔，而交感神经母细胞瘤主要出现在肾上腺和肾上腺周围区域。这些肿瘤具有重叠的组织病理学特征。据报道，罕见的交感神经母细胞瘤转移到鼻腔。PHOX2B已被证明对交感神经母细胞瘤具有相对特异性，但只有有限数量的嗅神经母细胞瘤病例进行了PHOX2B表达检测。本研究旨在探索MALAT1和PHOX2B在区分这两种实体中的潜在用途。针对嗅觉神经母细胞瘤（n=26）和交感神经母细胞瘤（n=52）创建了组织微阵列（TMA）。使用RNAScope技术通过原位杂交评估MALAT1lncRNA表达。通过Vectra多光谱成像系统扫描TMA载玻片，并使用inForm软件进行图像分析和定量。通过免疫组织化学分析PHOX2B表达。MALAT1在两种肿瘤类型中均显示主要的核表达，并且与交感神经母细胞瘤相比，MALAT1在嗅觉神经母细胞瘤中的表达高2倍（p<0.0001）。PHOX2B在大多数交感神经母细胞瘤中显示出核染色（51/52，98％），而只有1个嗅觉神经母细胞瘤（3.8％）对此标记物呈局部阳性。这些发现表明PHOX2B的免疫染色可能是区分这两种肿瘤类型的极好标记。
