Academic Department of Clinical Oncology, University of Nottingham, City Hospital Campus, Hucknall Road, Nottingham NG5 1PB, UK.
Br J Cancer. 2013 May 28;108(10):2097-105. doi: 10.1038/bjc.2013.166. Epub 2013 Apr 16.
The primary aim was to determine the prognostic significance of apoptosis in colorectal tumour cells and tumour-associated stroma. A secondary aim was to determine whether apoptosis was related to immune surveillance.
Immunohistochemistry was performed using monoclonal antibodies recognising cleaved caspase-3 (CC3), cleaved poly (ADP-ribose) polymerase (PARP), p53, Bcl2, MHC-II, B cells (CD16), macrophages (CD68) and T cells (CD3), on a tissue microarray of 462 colorectal tumours.
Kaplan-Meier analysis demonstrated that patients with high expression of CC3 in the tumour or CC3 or cleaved PARP in tumour-associated stroma have a good prognosis. This suggests that tumour stroma is promoting tumourigenesis and that high levels of death within the stroma breaks this link. CC3 levels in the tumour correlated with cleaved PARP and MHC-II expression but not with CD16, CD68, CD3, p53 or Bcl2 expression. CC3 levels on tumour-associated stroma also correlated with cleaved PARP and MHC-II expression but not with CD16, CD68, CD3, p53 or Bcl2 expression. Tumour cells express MHC-II in response to IFN-γ, suggesting that this may be one of the initiators of apoptosis within the good prognosis tumours. Although 73% of the MHC-II-positive tumour had high levels of apoptosis, many tumours had high levels of apoptosis in the absence of MHC-II, implying that this is only one of many causes of apoptosis within tumours. On multivariate analysis, using Cox's proportional hazards model, tumour stage, vascular invasion and expression of CC3 in tumour-associated stroma were shown to be independent markers of prognosis.
This study shows that a high level of apoptosis within colorectal tumour-associated stroma is an independent marker of good prognosis.
主要目的是确定结直肠肿瘤细胞和肿瘤相关基质中细胞凋亡的预后意义。次要目的是确定凋亡是否与免疫监视有关。
使用识别切割半胱氨酸天冬氨酸蛋白酶-3（CC3）、切割多聚（ADP-核糖）聚合酶（PARP）、p53、Bcl2、MHC-II、B 细胞（CD16）、巨噬细胞（CD68）和 T 细胞（CD3）的单克隆抗体，对 462 例结直肠肿瘤组织微阵列进行免疫组织化学染色。
Kaplan-Meier 分析表明，肿瘤中 CC3 高表达或肿瘤相关基质中 CC3 或切割 PARP 高表达的患者预后良好。这表明肿瘤基质促进了肿瘤的发生，而基质中高水平的死亡打破了这种联系。肿瘤中 CC3 水平与切割 PARP 和 MHC-II 表达相关，但与 CD16、CD68、CD3、p53 或 Bcl2 表达无关。肿瘤相关基质中 CC3 水平也与切割 PARP 和 MHC-II 表达相关，但与 CD16、CD68、CD3、p53 或 Bcl2 表达无关。肿瘤细胞表达 MHC-II 是对 IFN-γ的反应，这表明这可能是预后良好的肿瘤中凋亡的启动因素之一。尽管 73%的 MHC-II 阳性肿瘤有高水平的凋亡，但许多肿瘤在没有 MHC-II 的情况下也有高水平的凋亡，这意味着这只是肿瘤中凋亡的众多原因之一。多变量分析显示，使用 Cox 比例风险模型，肿瘤分期、血管侵犯和肿瘤相关基质中 CC3 的表达是独立的预后标志物。
本研究表明，结直肠肿瘤相关基质中高水平的凋亡是预后良好的独立标志物。
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