Characterization of rectal, proximal and distal colon cancers based on clinicopathological, molecular and protein profiles
Characterization of rectal, proximal and distal colon cancers based on clinicopathological, molecular and protein profiles
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DOI：
10.3892/ijo_00000720
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发表时间：
2010-09-01
影响因子：
5.2
通讯作者：
Lugli, A.
中科院分区：
文献类型：
--
作者：
Minoo, P.;Zlobec, I.;Lugli, A.
越来越多的证据表明，结直肠癌（CRC）应被视为一种异质性疾病，近端和远端CRC显示出多种生物学和临床差异。本研究的目的是建立一个临床病理学，分子和蛋白质的CRCs的基础上，他们的区域，从而提供深入了解其异质性。CRC患者（n=399）的临床病理和分子特征，包括K-RAS，BRAF和MSI状态进行了评估。还对肿瘤进行了50种免疫组织化学标记物的表达筛选，这些标记物与肿瘤进展或免疫应答中涉及的主要信号传导途径有关。与远端结肠和直肠相比，近端肿瘤显示出明显更大的肿瘤大小、更高的T分期、更高的肿瘤分级和更常见的粘液组织学亚型。BRAF突变和MSI高表型的频率在近端结肠癌中显著较高。10种肿瘤相关标志物（CDX 2、CD 44 v6、CD 44 s、TOPK、核B-catenin、pERK、APAF-1、E-cadherin、p21和bcl 2）和4种免疫反应标志物（CD 68、CD 163、FoxP 3和TIA-1）的区域表达存在显著差异。在多变量分析中，发现CD 44 s、CD 44 v6、核B-连环蛋白和CD 68表达最能区分左侧结肠癌和右侧结肠癌。肿瘤直径、pT分期和MSI状态最能区分右侧结肠癌和直肠癌，pT分期和E-钙粘蛋白最能区分左侧结肠癌和直肠癌。这些数据沿着存在不同区域胚胎起源和基因表达谱的现有证据，高度支持近端和远端CRC是不同临床病理实体的概念。
Accumulating evidence suggests that colorectal cancer (CRC) should be viewed as a heterogeneous disease, with proximal and distal CRCs showing multiple biological and clinical differences. The aim of this study was to develop a clinicopathological, molecular and protein profile for CRCs based on their region and thus providing insight into their heterogeneity. CRC patients (n=399) were evaluated for clinicopathologic and molecular features including K-RAS, BRAF and MSI status. Tumors were also screened for expression of 50 immunohistochemical markers linked to major signaling pathways involved in tumor-progression or immune response. Proximally located tumors show significantly larger tumor size, higher T-stage, higher tumor grade and more frequent mucinous histologic subtype compared to the distal colon and rectum. The frequency of BRAF mutation and MSI-high phenotype were significantly higher in proximal colon cancers. There is a significant difference in regional expression of 10 tumor-associated markers (CDX2, CD44v6, CD44s, TOPK, nuclear B-catenin, pERK, APAF-1, E-cadherin, p21 and bcl2) and 4 immune response markers (CD68, CD163, FoxP3 and TIA-1). In multivariate analysis CD44s, CD44v6, nuclear B-catenin and CD68 expression was found to best discriminate left- versus right-sided colon cancers. Tumor diameter, pT stage and MSI status best distinguish right-sided colon cancers from rectal cancers and pT stage and E-cadherin best discriminate left-sided colon cancers and rectal cancers. These data along with existing evidence for the presence of distinct regional embryological origin and gene expression profile are highly supportive of the concept that proximal and distal CRCs are distinct clinicopathologic entities.