Koelink P J, Sier C F M, Hommes D W, Lamers C B H W, Verspaget H W
Department of Gastroenterology-Hepatology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
Br J Cancer. 2009 Sep 1;101(5):765-73. doi: 10.1038/sj.bjc.6605220. Epub 2009 Aug 4.
Epithelial and stromal cells play an important role in the development of colorectal cancer (CRC). We aimed to determine the prognostic significance of both epithelial and stromal cell apoptosis in CRC.
Total apoptosis was determined by caspase-3 activity measurements in protein homogenates of CRC specimens and adjacent normal mucosa of 211 CRC patients. Epithelial apoptosis was determined by an ELISA specific for a caspase-3-degraded cytokeratin 18 product, the M30 antigen. Stromal apoptosis was determined from the ratio between total and epithelial apoptosis.
Epithelial and stromal apoptosis, as well as total apoptosis, were significantly higher in CRC compared with corresponding adjacent normal mucosa. Low total tumour apoptosis (< or = median caspase-3 activity) was associated with a significantly worse disease recurrence (hazard ratio (HR), 95% confidence interval (95% CI): 1.77 (1.05-3.01)), independent of clinocopathological parameters. Epithelial apoptosis was not associated with clinical outcome. In contrast, low stromal apoptosis (< or = median caspase-3/M30) was found to be an independent prognostic factor for overall survival, disease-free survival and disease recurrence, with HRs (95% CI) of 1.66 (1.17-2.35), 1.62 (1.15-2.29) and 1.69 (1.01-2.85), respectively.
Stromal apoptosis, in contrast to epithelial apoptosis, is an important factor with respect to survival and disease-recurrence in CRC.
上皮细胞和基质细胞在结直肠癌（CRC）的发生发展中起重要作用。我们旨在确定上皮细胞和基质细胞凋亡在CRC中的预后意义。
通过检测211例CRC患者的CRC标本及相邻正常黏膜蛋白匀浆中的半胱天冬酶-3活性来测定总凋亡。上皮细胞凋亡通过一种针对半胱天冬酶-3降解的细胞角蛋白18产物（M30抗原）的酶联免疫吸附测定（ELISA）来确定。基质细胞凋亡通过总凋亡与上皮细胞凋亡的比值来确定。
与相应的相邻正常黏膜相比，CRC中的上皮细胞和基质细胞凋亡以及总凋亡均显著更高。低总肿瘤凋亡（≤半胱天冬酶-3活性中位数）与疾病复发显著更差相关（风险比（HR），95%置信区间（95%CI）：1.77（1.05 - 3.01）），独立于临床病理参数。上皮细胞凋亡与临床结局无关。相反，低基质细胞凋亡（≤半胱天冬酶-3/M30中位数）被发现是总生存、无病生存和疾病复发的独立预后因素，HR（95%CI）分别为1.66（1.17 - 2.35）、1.62（1.15 - 2.29）和1.69（1.01 - 2.85）。
与上皮细胞凋亡相反，基质细胞凋亡是CRC生存和疾病复发的一个重要因素。
