Stromal staining for PINCH is an independent prognostic indicator in colorectal cancer
Stromal staining for PINCH is an independent prognostic indicator in colorectal cancer
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DOI：
10.1593/neo.04304
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发表时间：
2004-11-01
期刊：
影响因子：
4.8
通讯作者：
Sun, XF
中科院分区：
文献类型：
--
作者：
Gao, JF;Arbman, G;Sun, XF
特别有趣的新的富含半胱氨酸-组氨酸的蛋白质（PINCH），一种在整联蛋白和生长因子信号转导途径中起作用的LIM结构域衔接蛋白，在与许多常见癌症相关的基质中上调。这一发现表明PINCH可能参与促进支持肿瘤进展的肿瘤-基质相互作用，如果是这样，具有丰富PINCH基质染色的肿瘤可能具有更差的预后。为了验证这一假设，174例原发性结直肠腺癌与39例远处正常粘膜样本和26例淋巴结转移进行了免疫组化研究，并通过Western印迹分析和免疫荧光研究了7个额外的结肠肿瘤。PINCH蛋白在间质中的丰度从正常粘膜到原发性肿瘤再到转移灶逐渐增加（P <0.05），并且在浸润边缘比在肿瘤内间质中更强。PINCH的强基质免疫染色显示预测更差的结局（率比2.1，95% CI 1.16-3.37，P = 0.01），与Dukes分期、生长模式和肿瘤分化无关。在成纤维细胞、肌成纤维细胞和肿瘤血管系统的一定比例的内皮细胞中检测到PINCH，支持PINCH参与促进支持肿瘤进展的肿瘤-基质相互作用。有趣的是，PINCH的间质染色是结直肠癌的独立预后指标。
Particularly interesting new cysteine-histidine-rich protein (PINCH), a LIM domain adapter protein that functions in the integrin and growth factor signal transduction pathway, is upregulated in stroma associated with many common cancers. The finding suggested that PINCH may be involved in promoting tumor-stromal interactions that support tumor progression, and, if so, tumors with abundant PINCH stromal staining may have a worse prognosis. To test this hypothesis, 174 primary colorectal adenocarcinomas with 39 distant normal mucosa samples and 26 metastases in the lymph nodes were studied by immunohistochemistry, and 7 additional colon tumors were studied by Western blot analysis and immunofluorescence. The abundance of PINCH protein in stroma increased from normal mucosa to primary tumor to metastasis (P < .05), and was more intense at the invasive margin than it was in the intratumoral stroma. Strong stromal immunostaining for PINCH was shown to predict a worse outcome (rate ratio 2.1, 95% CI 1.16-3.37, P =.01), independent of Dukes stage, growth pattern, and tumor differentiation. PINCH was detected in fibroblasts, myofibroblasts, and a proportion of endothelial cells of the tumor vasculature, supporting the involvement of PINCH in promoting tumor-stromal interactions that support tumor progression. Interestingly, stromal staining for PINCH was an independent prognostic indicator in colorectal cancer.