Anoikis is a form of apoptosis induced when a cell loses contact with the extracellular matrix (ECM). Anoikis resistance is essential for metastasis formation, yet only detectable by in vitro experiments. We present a method for quantitation of putative anoikis-resistant (AR) subpopulations in colorectal carcinoma (CRC) and evaluate their prognostic significance. We studied 137 CRC cases and identified cell subpopulations with and without stromal or extracellular matrix (ECM) contact with hematoxylin-and-eosin-stained sections and immunohistochemistry for laminin and type IV collagen. Suprabasal cells of micropapillary structures and inner cells of cribriform and solid structures lacked both stromal contact and contact with ECM proteins. Apoptosis rate (M30) was lower in these subpopulations than in the other carcinoma cells, consistent with putative AR subpopulation. We determined the areal density of these subpopulations (number/mm2 tumor tissue), and their high areal density independently indicates low cancer-specific survival. In conclusion, we show evidence that subpopulations of carcinoma cells in micropapillary, cribriform, and solid structures are resistant to anoikis as shown by lack of ECM contact and low apoptosis rate. Abundance of these subpopulations is a new independent indicator of poor prognosis in CRC, consistent with the importance of anoikis resistance in the formation of metastasis.

中文翻译：

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结直肠癌中假定的耐厌氧反应的亚群：不良预后的标志。

失语症是细胞与细胞外基质（ECM）失去联系时诱导的凋亡形式。Anoikis耐药性对于转移形成至关重要，但只能通过体外实验检测到。我们提出了一种定量的结直肠癌（CRC）推定的抗厌氧反应（AR）亚群的方法，并评估它们的预后意义。我们研究了137例CRC病例，确定了有或没有基质或细胞外基质（ECM）与苏木精和曙红染色切片接触的细胞亚群，以及层粘连蛋白和IV型胶原的免疫组织化学。微乳头结构的上基底细胞以及筛状和固体结构的内部细胞缺乏基质接触和与ECM蛋白的接触。这些亚群的细胞凋亡率（M30）低于其他癌细胞，与推定的AR亚群一致。我们确定了这些亚群的面密度（数量/ mm2肿瘤组织），并且它们的高面密度独立表明了低的癌症特异性存活率。总之，我们显示出证据，表明微乳头状，筛状和固体结构中的癌细胞亚群对无神经细胞有抗药性，如缺乏ECM接触和低细胞凋亡率所显示。这些亚群的丰富是结直肠癌预后不良的新的独立指标，与无神经耐药性在转移形成中的重要性相一致。我们显示出证据，表明微乳头状，筛状和固体结构中的癌细胞亚群对无神经细胞有抗药性，如缺乏ECM接触和低细胞凋亡率所显示。这些亚群的丰富是结直肠癌预后不良的新的独立指标，与无神经耐药性在转移形成中的重要性相一致。我们显示出证据，表明微乳头状，筛状和固体结构中的癌细胞亚群对无神经细胞有抗药性，如缺乏ECM接触和低细胞凋亡率所显示。这些亚群的丰富是结直肠癌预后不良的新的独立指标，与无神经耐药性在转移形成中的重要性相一致。