Department of Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, United States of America; Department Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, United States of America.
Department of Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, United States of America.
Ann Diagn Pathol. 2020 Dec;49:151622. doi: 10.1016/j.anndiagpath.2020.151622. Epub 2020 Sep 7.
The skull base is the location of a wide variety of malignant tumors. Among them is sinonasal undifferentiated carcinoma (SNUC), a highly aggressive sinonasal neoplasm that was recently reclassified into subgroups of high-grade carcinomas with unique genomic events (e.g., SMARC-deficient carcinoma, nuclear protein in testis NUT carcinoma). Other high-grade carcinomas in this location are neuroendocrine carcinomas, sinonasal adenocarcinomas, and teratocarcinosarcomas. Given the rarity of these tumors, little transcriptomic data is available. The aim of this study was to characterize the immune-oncology gene expression profile in SNUC and other high-grade sinonasal carcinomas. Next-generation sequencing was performed in 30 high-grade sinonasal carcinoma samples using the HTG EdgeSeq Precision Immuno-Oncology Panel. Ingenuity pathway analysis was performed to understand the immunobiology, signaling, and functional perturbations during tumor development. The samples were divided into 3 groups: 21 SNUCs and SMARC-deficient sinonasal carcinomas; 5 high-grade neuroendocrine carcinomas (HGNECs), with small cell and large cell variants; and 4 high-grade sinonasal carcinomas (HGSNCs) of mixed histology (1 NUT carcinoma, 1 teratocarcinosarcoma, and 2 sinonasal adenocarcinomas). PRAME and ASCL1 emerged as upregulated transcripts with strong protein validation for SNUC and HGNEC; other upregulated candidates EZH2 and BRCA1 offer consideration for alternative targeted therapy, and downregulation of major histocompatibility complex molecules and chemokines represent another hurdle in the development of effective immunotherapy. This immune-oncology gene expression analysis of 3 groups of high-grade sinonasal carcinoma with emphasis on SNUC identified a number of differentially expressed transcripts reflecting effects on tumorigenesis. Identification of immune pathways should be further investigated for possible integration of immunotherapy into a multidisciplinary approach to these cancers and personalized treatment.
颅底是多种恶性肿瘤的位置。其中包括鼻腔鼻窦未分化癌（SNUC），这是一种高度侵袭性的鼻腔鼻窦肿瘤，最近被重新分类为具有独特基因组事件的高级别癌亚组（例如，SMARC 缺陷型癌、睾丸核蛋白 NUT 癌）。该部位的其他高级别癌包括神经内分泌癌、鼻腔鼻窦腺癌和胚胎性癌肉瘤。鉴于这些肿瘤的罕见性，可用的转录组数据很少。本研究的目的是描述 SNUC 和其他高级别鼻腔鼻窦癌的免疫肿瘤学基因表达谱。使用 HTG EdgeSeq Precision Immuno-Oncology Panel 在 30 个高级别鼻腔鼻窦癌样本中进行了下一代测序。进行了 Ingenuity 通路分析，以了解肿瘤发展过程中的免疫生物学、信号和功能改变。这些样本分为 3 组：21 个 SNUC 和 SMARC 缺陷型鼻腔鼻窦癌；5 个高级别神经内分泌癌（HGNEC），包括小细胞和大细胞变体；以及 4 个混合组织学的高级别鼻腔鼻窦癌（HGSNC）（1 个 NUT 癌、1 个胚胎性癌肉瘤和 2 个鼻腔鼻窦腺癌）。PRAME 和 ASCL1 作为 SNUC 和 HGNEC 上调转录本出现，具有强烈的蛋白验证；其他上调候选物 EZH2 和 BRCA1 为替代靶向治疗提供了考虑，主要组织相容性复合物分子和趋化因子的下调代表了开发有效免疫疗法的另一个障碍。这项针对强调 SNUC 的 3 组高级别鼻腔鼻窦癌的免疫肿瘤学基因表达分析确定了许多反映肿瘤发生影响的差异表达转录本。免疫途径的鉴定应进一步研究，以将免疫疗法纳入这些癌症的多学科方法和个体化治疗中。
