Differential diagnostic and functional role of the multi-marker phenotype CDX2/CK20/CK7 in colorectal cancer stratified by mismatch repair status

Differential diagnostic and functional role of the multi-marker phenotype CDX2/CK20/CK7 in colorectal cancer stratified by mismatch repair status
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DOI:
10.1038/modpathol.2008.117
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发表时间:
2008-11-01
期刊:
影响因子:
7.5
通讯作者:
Terracciano, Luigi Maria
Terracciano, Luigi Maria
中科院分区:
医学1区
文献类型:
--
作者:
Lugli, Alessandro;Tzankov, Alexandar;Terracciano, Luigi Maria

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区分结直肠癌与其他部位的原发肿瘤可能具有挑战性。通常需要一组免疫组织化学蛋白质标记来区分这些实体。根据错配修复状态,结直肠癌中的蛋白质表达存在显着差异,并且在错配修复良好或缺陷的肿瘤中也存在异质性。本研究的目的是系统分析常用多标记表型 CK20/CK7/CDX2 对按错配修复状态分层的大量结直肠癌的诊断和预后作用。使用组织微阵列对 1197 例错配修复良好和 223 例错配修复缺陷的结直肠癌进行 CK20、CK7 和 CDX2 的免疫组织化学分析。探索了 CK20/CK7/CDX2 的多标记组合。对标记物的单变量和多变量分析评估了它们与几个临床病理终点(即T分期、N分期、肿瘤分级、血管侵犯、瘤内淋巴细胞和生存)的关联。 CK20 和 CDX2 阴性的多标志物表型在错配修复缺陷的结直肠癌中比在错配修复充分的结直肠癌中更常见(分别为 19.3 vs 7.5% 和 21.6 vs 6.7%;P
The differentiation of colorectal cancer from primary tumors at other sites can be challenging. Often a panel of immunohistochemical protein markers is needed to distinguish between these entities. Protein expression differs significantly in colorectal cancer depending on mismatch repair status and is also heterogeneous among mismatch repair-proficient or -deficient tumors. The aim of this study was to systematically analyze the diagnostic and prognostic role of the commonly used multi-marker phenotype CK20/CK7/CDX2 on a large series of colorectal cancers stratified by mismatch repair status. The immunohistochemical analysis of CK20, CK7 and CDX2 was performed on 1197 mismatch repair-proficient and 223 mismatch repair-deficient colorectal cancers using a tissue microarray. Multi-marker combinations of CK20/CK7/CDX2 were explored. Univariate and multivariable analysis of the markers was evaluated for their association with several clinico-pathological end points namely T stage, N stage, tumor grade, vascular invasion, intratumoral lymphocytes and survival. Multimarker phenotypes with CK20 and CDX2 negativity were more frequently found in mismatch repair-deficient than in mismatch repair-proficient colorectal cancer (19.3 vs 7.5% and 21.6 vs 6.7%, respectively; P