Sheehan Katherine M, O'Donovan Deirdre G, Fitzmaurice Gillian, O'Grady Anthony, O'Donoghue Diarmuid P, Sheahan Kieran, Byrne Michael F, Conroy Ronan M, Kay Elaine W, Murray Frank E
Department of Pathology, Royal College of Surgeons in Ireland and Beaumont Hospital, Dublin, Ireland.
Eur J Gastroenterol Hepatol. 2003 Apr;15(4):375-80. doi: 10.1097/00042737-200304000-00007.
Fas ligand (FasL) is an important mediator of immune function and induces apoptosis by binding to its receptor Fas on sensitized cells. It has recently been shown that malignancies may express FasL and acquire immune privilege by inducing apoptosis of lymphocytes. Acquired resistance to Fas mediated apoptosis is known to be an early event in carcinogenesis. The aim of this study was to determine the extent of FasL expression in patients with colorectal cancer and examine its relationship with several prognostic pathological features and survival.
Sixty-eight patients (median age 66 years) with colorectal cancer, whose diagnosis was made between 1988 and 1991 and in whom long-term follow-up was available, were evaluated. The tumours were of varying stages at diagnosis (eight Dukes' A, 28 Dukes' B, 23 Dukes' C and nine Dukes' D). The expression of FasL was detected immunohistochemically with a rabbit polyclonal IgG using the DAKO EnVision+ System. The specificity of FasL binding was confirmed by pre-incubation of the antibody with the immunizing peptide prior to staining. The relationship with several pathological features was determined using Kendall's tau-b correlation. Overall survival was estimated using the Kaplan-Meier product limit curves. Differences in observed survival were tested for statistical significance using the Mantel-Haenszel log rank test. Both the extent and intensity of staining were graded by a blinded observer.
FasL was predominantly expressed in tumour epithelial cells in 88% of the cases. The positive staining of tumours varied in extent. FasL staining was higher in earlier Dukes' stage tumours in that the extent of FasL staining negatively correlated with Dukes' stage (Kendall tau-b = -0.22, P = 0.038). Consistent with this, the overall survival was better with a greater extent of FasL expression (log rank chi2 = 5.68, P = 0.017). There was a lower extent of FasL expression in mucinous adenocarcinomas (Kendall tau-b = 0.288, P = 0.01) and in those tumours with neural invasion (Kendall tau-b = -0.26, P = 0.03). No relationship was detected between FasL and tumour site, size, margin, differentiation, vascular invasion, necrosis or Crohn's-like reaction.
FasL is widely expressed in colorectal cancers. This finding suggests that the extent of FasL expression in colorectal tumours is directly related to patients' survival.
Fas配体（FasL）是免疫功能的重要介质，通过与致敏细胞上的受体Fas结合诱导细胞凋亡。最近研究表明，恶性肿瘤可能表达FasL，并通过诱导淋巴细胞凋亡获得免疫特权。已知对Fas介导的细胞凋亡产生获得性抗性是致癌过程中的早期事件。本研究的目的是确定结直肠癌患者中FasL的表达程度，并研究其与几种预后病理特征及生存率的关系。
对68例1988年至1991年间确诊且有长期随访资料的结直肠癌患者（中位年龄66岁）进行评估。诊断时肿瘤处于不同分期（8例Dukes'A期、28例Dukes'B期、23例Dukes'C期和9例Dukes'D期）。使用DAKO EnVision+系统，采用兔多克隆IgG免疫组化检测FasL的表达。在染色前，通过将抗体与免疫原性肽预孵育来确认FasL结合的特异性。使用Kendall's tau-b相关性分析其与几种病理特征的关系。采用Kaplan-Meier乘积限界曲线估计总生存率。使用Mantel-Haenszel对数秩检验对观察到的生存率差异进行统计学显著性检验。染色的范围和强度均由一位不知情的观察者进行分级。
88%的病例中FasL主要表达于肿瘤上皮细胞。肿瘤的阳性染色范围各不相同。FasL染色在较早的Dukes分期肿瘤中更高，因为FasL染色范围与Dukes分期呈负相关（Kendall tau-b = -0.22，P = 0.038）。与此一致，FasL表达范围越大，总生存率越好（对数秩chi² = .68，P = 0.017）。黏液腺癌（Kendall tau-b = 0.288，P = 0.01）和有神经侵犯的肿瘤（Kendall tau-b = -0.26，P = 0.03）中FasL表达范围较低。未检测到FasL与肿瘤部位、大小、切缘、分化程度、血管侵犯、坏死或克罗恩样反应之间的关系。
FasL在结直肠癌中广泛表达。这一发现表明结直肠癌中FasL的表达程度与患者生存率直接相关。
Zotero 插件