Role of phosphorylated Smad3 signal components in intraductal papillary mucinous neoplasm of pancreas
Role of phosphorylated Smad3 signal components in intraductal papillary mucinous neoplasm of pancreas
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DOI：
10.1016/j.hbpd.2020.05.007
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发表时间：
2020-12-01
影响因子：
3.3
通讯作者：
Okazaki, Kazuichi
中科院分区：
文献类型：
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作者：
Hori, Yuichi;Ikeura, Tsukasa;Okazaki, Kazuichi
背景：恶性导管内乳头状黏液性肿瘤(IPMN)预后不良。IPMN的致癌机制尚不清楚。本研究的目的是阐明IPMN癌变过程中磷酸化Smad3信号通路的转变。方法：采用免疫组织化学方法，检测2010-2013年间我所手术切除的51例IPMN标本中pSmad3C和pSmad3L的表达。结果：pSmad3C在低度不典型增生、高度不典型增生和浸润性癌中的平均免疫染色指数分别为79.2%、74.9%和42.0%(P<0.01)，PS-Mad3L的平均免疫染色指数分别为3.4%、4.3%和42.4%(P<；0.01)。PSmad3C与c-Myc的表达呈负相关(P<；0.001，r=-0.615)，pSmad3L与c-Myc的表达呈正相关(P<；0.001，r=0.696)。PSmad3C与Ki-67表达呈负相关(P<；0.01，r=-0.610)，pSmad3L与Ki-67表达呈正相关(P<；0.01，r=0.731)。在pSmad3L阳性癌细胞中，P-JNK阳性细胞较多见。未复发组和复发组pSmad3L/pSmad3C比值的中位数分别为0.58(0.05~0.93)、3.83(0.85~5.96)(P=0.02)。C-Myc在无复发组和复发组的中位免疫染色指数分别为2.91(0~36.9)和82.1(46.2~97.1)(P=0.02)。Ki-67在无复发组和复发组的中位免疫染色指数分别为12.9(5.7~30.8)和90.9(52.9~98.5)(P=0.02)。结论：恶性IPMN中pSmad3L表达上调。PSmad3L/pSmad3C比值可能是IPMN的一个有价值的预后因素。(C)2020年浙江大学医学院附属第一医院在中国。爱思唯尔出版，版权所有。
Background: Malignant intraductal papillary mucinous neoplasm (IPMN) has poor prognosis. The carcinogenesis of IPMN is not clear. The aim of this study was to clarify transitions in phosphorylated Smad3 signaling during IPMN carcinogenesis.Methods: By using immunohistochemistry, we examined the expression of pSmad3C and pSmad3L from 51 IPMN surgical specimens resected at our institution between 2010 and 2013. We also examined the expression of Ki-67, c-Myc and p-JNK.Results: The median immunostaining index of pSmad3C was 79.2% in low-grade dysplasia, 74.9% in high-grade dysplasia, and 42.0% in invasive carcinoma (P < 0.01), whereas that of pS-mad3L was 3.4%, 4.3%, and 42.4%, respectively (P < 0.01). There was a negative relationship between the expression of pSmad3C and c-Myc (P < 0.001, r = -0.615) and a positive relationship between the expression of pSmad3L and c-Myc (P < 0.001, r = 0.696). Negative relationship between the expression of pSmad3C and Ki-67 (P < 0.01, r = -0.610) and positive relationship between the expression of pSmad3L and Ki-67 (P < 0.01, r = 0.731) were confirmed. p-JNK-positive cells were frequently observed among pSmad3L-positive cancer cells. The median of pSmad3L/pSmad3C ratio in the non-recurrence group and the recurrence group were 0.58 (range, 0.05-0.93), 3.83 (range, 0.85-5.96), respectively (P = 0.02). The median immunostaining index of c-Myc in the non-recurrence group and the recurrence group were 2.91 (range, 0-36.9) and 82.1 (range, 46.2-97.1), respectively (P = 0.02). The median immunostaining index of Ki-67 in the non-recurrence group and the recurrence group were 12.9 (range 5.7-30.8) and 90.9 (range 52.9-98.5), respectively (P = 0.02).Conclusions: pSmad3L was upregulated in malignant IPMN. pSmad3L/pSmad3C ratio may be a useful prognostic factor in IPMN. (C) 2020 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.