PO.MCB07.03 · 分子与细胞生物学

唾液腺导管癌中EGR1表达与神经周围侵犯：SDCDN与SDCXPA的比较

EGR1 Expression and Perineural Invasion in Salivary Duct Carcinoma: A comparison of SDCDN and SDCXPA

编号 5948 展板 3 时间 4/21 02:00–05:00 区域 Section 22 主讲 Airi Sakyo, MD;PhD

分会场 Mechanisms and Dynamics of Gene Expression

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作者与单位 Authors & Affiliations

Airi Sakyo¹, Eijitsu Ryo², Seiichi Yoshimoto³, Go Omura³, Chihiro Fushimi³, Toshihiko Sakai³, Yoshifumi Matsumoto¹, Azusa Sakai³, Kohtaro Eguchi³, Yo Suzuki¹, Kazuki Yokoyama⁴, Yoshitaka Honma⁴, Yasushi Yatabe⁵, Fumihiko Matsumoto¹, Taisuke Mori⁵

¹Otorhinolaryngology, Juntendo University Faculty of Medicine, Tokyo, Japan,²Division of Molecular Pathology, National Cancer Center Research Institute, Tokyo, Japan,³Head and Neck Surgery, National Cancer Center Hospital, Tokyo, Japan,⁴Department of Head and Neck, Esophageal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan,⁵Diagnostic Pathology, National Cancer Center Hospital, Tokyo, Japan

摘要 Abstract

中文摘要

唾液腺导管癌(SDC)主要分为原发性(SDCDN)或多形性腺瘤恶变(SDCXPA)。既往报道表明SDCXPA中HMGA2和PLAG1融合事件的频率更高。由于对新治疗策略的指导有限，手术切除仍是主要干预措施。然而，频繁复发和转移的困难管理凸显了创新治疗的必要性。本研究旨在探讨SDC的特征，包括神经周围侵犯(PNI)，并阐明其致癌机制和不良预后因素。我们分析了2014年至2023年在国立癌症中心医院诊断的52例SDC患者。为比较基因表达谱，我们进行了免疫组化染色，包括Her2、雄激素受体(AR)、PLAG1和HMGA2，随后对30例进行了人表皮生长因子受体2(HER2)原位杂交和RNA测序。差异分析鉴定了接受免疫组化染色和统计分析的基因。基于使用PLAG1和HMGA2的组织学分类，52例被分类为26例(50%)SDCDN和26例(50%)SDCXPA。与SDCXPA相比，SDCDN显示出更高的神经周围、静脉和淋巴侵犯率(分别为P=.0005、.0294和.0044)。基因表达谱分析揭示了这些亚型之间的聚类倾向。聚焦PNI，在浸润神经周围组织的肿瘤部分中早期生长反应1的基因表达降低，表明呈负相关(P<.0001)。类似地，ARID1A表达在具有神经周围侵犯病例的肿瘤区域升高；然而，免疫组化分析显示神经周围和非神经周围区域之间无差异。此外，RNA测序在SDC中鉴定出三个新的融合基因。总之，观察到基于分子和病理特征的SDCDN与SDCXPA之间的临床差异。我们发现早期生长反应1-脑源性神经营养因子连接了癌细胞与神经之间在SDC PNI中的串扰，为未来的治疗和预后因素提供了见解。

查看英文原文 English abstract

Salivary duct carcinoma (SDC) is primarily categorized as de novo (SDCDN) or ex pleomorphic adenoma (SDCXPA). Previous reports indicate a higher frequency of HMGA2 and PLAG1 fusion events in SDCXPA. Surgical resection remains the main intervention due to limited guidance on new treatment strategies. However, frequent recurrence and challenging management of metastasis highlight the necessity for innovative treatments. This study aimed to investigate SDC characteristics, including perineural invasion (PNI), and elucidate its carcinogenic mechanisms and adverse prognostic factors. We analyzed 52 patients with SDC diagnosed in the National Cancer Center Hospital from 2014 to 2023. To compare gene expression profiles, we performed immunohistochemical staining, including Her2, androgen receptor (AR), PLAG1, and HMGA2, followed by human epidermal growth factor receptor 2 (HER2) in situ hybridization and RNA sequencing of 30 cases. Differential analysis identified genes subjected to immunohistochemical staining and statistical analysis. Based on histologic classification using PLAG1 and HMGA2, 52 cases were classified as 26 cases (50%) SDCDN and 26 cases (50%) SDCXPA. Compared with SDCXPA, SDCDN showed higher perineural, venous, and lymphatic invasion rates (P = .0005, .0294, and .0044, respectively). Genetic expression profiling revealed clustering tendencies between these subtypes. Focusing on PNI, gene expression was decreased in early growth response 1 in tumor portions infiltrating perineural tissues, indicating a negative correlation (P < .0001). Similarly, ARID1A expression was elevated in tumor regions of cases with perineural invasion; however, immunohistochemical analysis showed no difference between perineural and non-perineural areas. Furthermore, RNA sequencing identified three novel fusion genes in SDC. In conclusion, clinical disparities between SDCDN and SDCXPA based on molecular and pathological features were observed. We found early growth response 1-brain-derived neurotrophic factor-linking crosstalk between cancer cells and nerves for PNI in SDC, offering insights into future treatment and prognostic factors.

利益披露 Disclosure

A. Sakyo, None.. E. Ryo, None.. S. Yoshimoto, None.. G. Omura, None.. C. Fushimi, None.. T. Sakai, None.. Y. Matsumoto, None.. A. Sakai, None.. K. Eguchi, None.. Y. Suzuki, None.. K. Yokoyama, None.. Y. Honma, None.. Y. Yatabe, None.. F. Matsumoto, None.. T. Mori, None.

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