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涎腺腺样囊性癌中MYB-NFIB嵌合基因表达、肿瘤血管生成及增殖的研究

Study of MYB-NFIB chimeric gene expression, tumor angiogenesis, and proliferation in adenoid cystic carcinoma of salivary gland.

作者信息

Ono Junya, Okada Yasuo

机构信息

Field of Oral and Maxillofacial Imaging and Histopathological Diagnostics, Histopathology of Pathogenic Mechanisms, Course of Applied Science, The Nippon Dental University Graduate School of Life Dentistry at Niigata, 1-8 Hamaura-cho, Chuo-ku, Niigata, Niigata, 951-8580, Japan.

Department of Pathology, The Nippon Dental University School of Life Dentistry at Niigata, 1-8 Hamaura-cho, Chuo-ku, Niigata, Niigata, 951-8580, Japan.

出版信息

Odontology. 2018 Jul;106(3):238-244. doi: 10.1007/s10266-017-0326-1. Epub 2017 Dec 14.

DOI:10.1007/s10266-017-0326-1
PMID:29243184
Abstract

Adenoid cystic carcinoma (ACC) is one of the common malignant tumors in salivary glands, and the clinical prognosis is poor with frequent distant metastasis which may lead to death. Expression of the MYB-NFIB chimeric gene in ACC has been reported recently. MYB is an oncogene with transcription regulating functions, and NFIB encodes nuclear transcription factor although detailed functions are unknown. This study investigated whether MYB-NFIB chimeric gene expression affects tumor angiogenesis and proliferation in salivary gland ACC. In 26 salivary gland ACC cases, MYB-NFIB chimeric gene expression was analyzed by RT-PCR and direct sequencing. Immunohistochemical studies for CD31, vascular endothelial growth factor (VEGF) and Ki-67 were performed. Tumor angiogenesis was evaluated by blood vessel (CD31-positive) density and tumor proliferation by Ki-67 labeling index, and the relationship with MYB-NFIB chimeric gene expression was analyzed. MYB-NFIB chimeric gene expression was detected in nine of 26 ACC cases. Blood vessel density was significantly higher in chimeric gene-expressing cases compared to non-expressing cases. VEGF score tended to be higher in chimeric gene-expressing cases than in non-expressing cases, while Ki-67 labeling index was not significantly different. The number of chimeric gene-expressing cases increased with age, peaking in the sixties age group and declining thereafter, while the number of non-expressing cases increased with age continuously. In ACC, blood vessel density was significantly higher in MYB-NFIB chimeric gene-expressing cases compared to non-expressing cases, which may be due to higher VEGF production capability. MYB-NFIB chimeric gene expression may also be related to the onset age of ACC.

摘要

腺样囊性癌(ACC)是涎腺常见的恶性肿瘤之一,临床预后较差,常发生远处转移,可导致死亡。最近有报道称MYB-NFIB嵌合基因在ACC中表达。MYB是一种具有转录调节功能的癌基因,NFIB编码核转录因子,但其具体功能尚不清楚。本研究调查了MYB-NFIB嵌合基因表达是否影响涎腺ACC的肿瘤血管生成和增殖。对26例涎腺ACC病例进行RT-PCR和直接测序分析MYB-NFIB嵌合基因表达。进行CD31、血管内皮生长因子(VEGF)和Ki-67的免疫组织化学研究。通过血管(CD31阳性)密度评估肿瘤血管生成,通过Ki-67标记指数评估肿瘤增殖,并分析其与MYB-NFIB嵌合基因表达的关系。26例ACC病例中有9例检测到MYB-NFIB嵌合基因表达。与未表达病例相比,表达嵌合基因的病例血管密度显著更高。表达嵌合基因的病例VEGF评分倾向于高于未表达病例,而Ki-67标记指数无显著差异。表达嵌合基因的病例数随年龄增加而增加,在60岁年龄组达到峰值,此后下降,而未表达病例数随年龄持续增加。在ACC中,与未表达病例相比,表达MYB-NFIB嵌合基因的病例血管密度显著更高,这可能是由于VEGF产生能力更高。MYB-NFIB嵌合基因表达也可能与ACC的发病年龄有关。

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