Lyall Matthew S, Dundas Sinclair R, Curran Stephanie, Murray Graeme I
Department of Pathology, University of Aberdeen, Aberdeen, UK.
Clin Cancer Res. 2006 Feb 15;12(4):1184-91. doi: 10.1158/1078-0432.CCR-05-1864.
Colorectal cancer is one of the most common forms of cancer in developed nations and the incidence of this disease is increasing. There is a need to further stratify prognostically distinct groups of colorectal cancer, and the purpose of this study was to identify prognostically significant immunohistochemical marker profiles in colorectal cancer.
In this study, a range (n = 23) of markers [pRb, p16, p21, p27, p53, proliferating cell nuclear antigen, cyclin D1, bcl-2, epidermal growth factor receptor, C-erb-B2, topoisomerase-I, liver fatty acid-binding protein, matrix metalloproteinases (MMP) 1-3, 7, 9, and 13, MT1-MMP, MT2-MMP, and tissue inhibitors of MMP 1-3] of putative prognostic significance have been investigated by immunohistochemistry on formalin-fixed, wax-embedded sections in a series (n = 90) of stage III (Dukes C) colorectal cancers. An immunohistochemical score based on the intensity of immunoreactivity and, where relevant, the proportion of immunoreactive cells was established for each marker.
Unsupervised two-dimensional hierarchical cluster analysis identified three distinct cluster groups (designated groups 1-3) with different marker profiles. There were significant survival differences between groups 1 and 2 (log rank = 11.48; P = 0.0007) and between groups 1 and 3 (log rank = 8.32; P = 0.0039). Multivariate analysis showed that the complete marker profile was independently the most significant prognostic factor (hazard ratio, 2.27; 95% confidence interval, 1.15-4.48; P = 0.004).
This study has identified an immunohistochemical marker profile of colorectal cancer and showed that it is an independent indicator of prognosis in this type of cancer.
结直肠癌是发达国家最常见的癌症形式之一，且该疾病的发病率正在上升。有必要进一步对预后不同的结直肠癌组进行分层，本研究的目的是确定结直肠癌中具有预后意义的免疫组化标志物谱。
在本研究中，通过免疫组化对一系列（n = 90）III期（Dukes C期）结直肠癌的福尔马林固定、石蜡包埋切片研究了一系列（n = 23）具有潜在预后意义的标志物[pRb、p16、p21、p27、p53、增殖细胞核抗原、细胞周期蛋白D1、bcl-2、表皮生长因子受体、C-erb-B2、拓扑异构酶-I、肝脂肪酸结合蛋白、基质金属蛋白酶（MMP）1 - 3、7、9和13、MT1-MMP、MT2-MMP以及MMP 1 - 3的组织抑制剂]。为每个标志物建立了基于免疫反应强度以及相关情况下免疫反应细胞比例的免疫组化评分。
无监督二维层次聚类分析确定了具有不同标志物谱的三个不同聚类组（命名为1 - 3组）。1组和2组之间（对数秩 = 11.48；P = 0.0007）以及1组和3组之间（对数秩 = 8.32；P = 0.0039）存在显著的生存差异。多变量分析表明，完整的标志物谱独立地是最显著的预后因素（风险比，2.27；95%置信区间，1.15 - 4.48；P = 0.004）。
本研究确定了结直肠癌的免疫组化标志物谱，并表明它是这类癌症预后的独立指标。
