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胰腺导管内乳头状黏液性肿瘤壁结节中SLC2A1/GLUT1的表达

SLC2A1/GLUT1 expression in mural nodules of intraductal papillary mucinous neoplasm of the pancreas.

作者信息

Oda Yasunori, Aishima Shinichi, Shindo Koji, Fujino Minoru, Mizuuchi Yusuke, Hattori Masami, Miyazaki Tetsuyuki, Tanaka Masao, Oda Yoshinao

机构信息

Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.

Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.

出版信息

Hum Pathol. 2017 Jul;65:71-78. doi: 10.1016/j.humpath.2017.03.008. Epub 2017 Apr 12.

Abstract

In intraductal papillary mucinous neoplasms (IPMNs), the presence of a mural nodule showing a papillary or nodular proliferation of tumor cells in the dilated pancreatic duct is an indication for resection of IPMN. Solute carrier family 2, facilitated glucose transporter member 1, known as glucose transporter type 1 (SLC2A1/GLUT1) mediates cellular glucose uptake in many carcinomas and is correlated with increased F-fluorodeoxyglucose (F-FDG) uptake. We examined SLC2A1/GLUT1 expression in the mural nodules of 180 IPMN specimens to distinguish malignant/benign tumors. A mural nodule was detected in 80 (44.4%) of the IPMNs, and was detected in 18.6% (13/70) of the IPMN-low (dysplasia) specimens, 36.1% (13/36) of the IPMN-int, 93.3% (28/30) of the IPMN-high, and 59.1% (26/44) of the IPMN-inv (with an associated invasive carcinoma) specimens. The sensitivity for detecting mural nodules was 81.7% by endoscopic ultrasonography, 70% by contrast-enhanced computed tomography and 54% by endoscopic retrograde cholangiopancreatography. SLC2A1/GLUT1 expression in the mural nodules was recognized in the basal and basolateral cytomembrane of tumor cells and was expressed in 15.4% (2/13) of the IPMN-low, 15.4% (2/13) of the IPMN-int, 71.4% (20/28) of the IPMN-high and 84.6% (22/26) of the IPMN-inv groups. The SLC2A1/GLUT1 expression was significantly higher in the IPMN-high and IPMN-inv mural nodules than in those of the IPMN-low and IPMN-int groups. Our findings suggest that SLC2A1/GLUT1 is expressed late in the adenoma-carcinoma sequence during carcinogenesis in IPMN, and SLC2A1/GLUT1 act as therapeutic target for malignant IPMN.

摘要

在导管内乳头状黏液性肿瘤(IPMN)中,扩张的胰管内出现显示肿瘤细胞呈乳头状或结节状增殖的壁结节是IPMN切除的指征。溶质载体家族2,易化葡萄糖转运蛋白成员1,即葡萄糖转运蛋白1型(SLC2A1/GLUT1),在许多癌症中介导细胞对葡萄糖的摄取,并与氟代脱氧葡萄糖(F-FDG)摄取增加相关。我们检测了180例IPMN标本壁结节中SLC2A1/GLUT1的表达,以区分恶性/良性肿瘤。80例(44.4%)IPMN中检测到壁结节,在低级别(发育异常)IPMN标本的18.6%(13/70)、中级IPMN的36.1%(13/36)、高级别IPMN的93.3%(28/30)以及伴有浸润性癌的IPMN(IPMN-inv)标本的59.1%(26/44)中检测到壁结节。内镜超声检测壁结节的敏感性为81.7%,对比增强计算机断层扫描为70%,内镜逆行胰胆管造影为54%。壁结节中SLC2A1/GLUT1表达在肿瘤细胞的基底和基底外侧细胞膜中可见,在低级别IPMN组的15.4%(2/13)、中级IPMN组的15.4%(2/13)、高级别IPMN组的71.4%(20/28)以及IPMN-inv组的84.6%(22/26)中表达。SLC2A1/GLUT1在高级别IPMN和IPMN-inv壁结节中的表达显著高于低级别IPMN和中级IPMN组。我们的研究结果表明,SLC2A1/GLUT1在IPMN癌变过程中的腺瘤-癌序列中表达较晚,且SLC2A1/GLUT1可作为恶性IPMN的治疗靶点。

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