Prevalent and up-regulated vimentin expression in micropapillary components of lung adenocarcinomas and its adverse prognostic significance
Prevalent and up-regulated vimentin expression in micropapillary components of lung adenocarcinomas and its adverse prognostic significance
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DOI：
10.1111/pin.12257
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发表时间：
2015-04-01
影响因子：
2.2
通讯作者：
Satoh, Yukitoshi
中科院分区：
文献类型：
--
作者：
Nakashima, Hiroyasu;Jiang, Shi-Xu;Satoh, Yukitoshi
肺腺癌伴微乳头状成分（AC-MPC）恶性程度增高的因素尚不清楚。在基于二维凝胶电泳的蛋白质组学上，AC-MPC和常规腺癌（CAC）之间差异表达超过1.5倍的19种蛋白质;特别是其中一种蛋白质波形蛋白在AC-MPC中上调3.5倍。随后通过免疫组化对101例不同分期的AC-MPC和119例不同分期的CAC进行半定量研究，结果显示95例MPC中有波形蛋白表达，（94.1%）AC-MPC的阳性表达率高于高、中分化CAC及AC-MPC的背景非MPC（P < 0.0001），但与低分化CAC比较差异无显著性（P = 0.561）。即使在AC-MPC实体中，波形蛋白的高表达也与更频繁的血管侵犯和更先进的淋巴结转移相关（P < 0.02），多因素分析显示波形蛋白的高表达和更差的淋巴结状态是不良预后的独立指标（P < 0.048）。结论：波形蛋白在MPC中普遍表达且表达显著上调，这可能反映了MPC分化不良或去分化的生物学本质，这可能与MPC侵袭性的获得和增强以及随之而来的恶性程度的增加有关。
The factors conferring the increased malignancy on lung adenocarcinoma with micropapillary component (AC-MPC) remain to be elucidated. On proteomics based on 2-dimensional gel electrophoresis, 19 proteins differentially expressed by more than 1.5-fold between AC-MPC and conventional adenocarcinoma (CAC); in particular, vimentin, one of the proteins, was 3.5-fold up-regulated in AC-MPC. Subsequent semi-quantitative investigation by immunohistochemistry with large cohorts comprised 101 AC-MPC and 119 CAC, respectively, of different stages revealed that vimentin was expressed in MPC of 95 (94.1%) AC-MPC and the expression scores were higher than those of well- and moderately differentiated CAC, as well as the background non-MPC of the AC-MPC (P < 0.0001), but not significantly different from those of poorly differentiated CAC (P = 0.561). Even within the AC-MPC entity, higher vimentin expression was correlated with more frequent vascular invasion and more advanced node metastasis (P < 0.02), and multivariate analysis showed that high vimentin expression and worse node statuses were independent indicators of adverse prognosis (P < 0.048). In conclusion, vimentin expression is prevalent and markedly up-regulated in MPC, which might reflect the biological essence of poorer differentiation or dedifferentiation of MPC, and this might have a role in the acquisition and increase of invasiveness and consequent more malignant nature of MPC.