Vera-Sempere F J, Burgos J S, Botella M S, Morera C
Service of Pathology II, Laboratory of Molecular Pathology, Hospital La Fe, Medical School of Valencia University, Spain.
Histol Histopathol. 1997 Jan;12(1):9-18.
Expression of Bcl-2 is associated with inhibition of apoptosis and extension of cell survival. In vitro Bcl-2 protein expression is up-regulated by the EBV-latency associated antigen latent membrane protein (LMP-1). We have investigated the relationship between the presence of EBV-DNA screened by means of sensitive nested-PCR, nasopharyngeal carcinoma (NPC) histological types according to two different schemata (WHO and Micheau classifications) and Bcl-2-124 immunohistochemical expression in 55 biopsy samples of NPC. EBV genome was detected in 100% of samples with sufficient DNA quality to support the previous view that all types of NPC are variants of EBV-infected neoplasia. Bcl-2 was observed in the basal layer of normal nasopharyngeal mucosa and also at cytoplasmic level in 42 of 55 (76.4%) NPC cases. Mitotic neoplastic cells usually showed strong cytoplasmic and chromosomal staining, a finding not well referred to previously. Bcl-2 expression was significantly associated (p<0.05) to undifferentiated NPC (UNPC) when a histological classification with only two major microscopical types was applied. No close correlations were found between the presence of EBV-DNA, NPC location, clinical stage and age or sex of the patients in relation to Bcl-2 positive expression. However, when comparing Bcl-2 expression and known survival mean of the patients, significant differences were observed (p<0.001) so that mean survivals were 31.1, 24.4, 52.2 and 54.1 months respectively for NPC patients with -, +, ++ and Bcl-2 immunoreactivity. Nevertheless this better clinical outcome in Bcl-2 NPC positive cases may depend on the histological type due to close relationship with UNPC. Only studies of larger series with long-term follow-up and multivariate analyses may document whether Bcl-2 expression is an independent prognostic marker in the evolution of NPC patients.
Bcl-2的表达与细胞凋亡的抑制及细胞存活期的延长相关。在体外，EB病毒潜伏相关抗原潜伏膜蛋白1（LMP-1）可上调Bcl-2蛋白的表达。我们采用敏感的巢式聚合酶链反应（PCR）检测EB病毒DNA的存在情况，根据两种不同的分类方法（世界卫生组织和米肖分类法）对鼻咽癌（NPC）的组织学类型进行分类，并对55例NPC活检样本进行Bcl-2-124免疫组化表达研究。在所有DNA质量足以支持先前观点（即所有类型的NPC都是EB病毒感染性肿瘤的变体）的样本中，均检测到了EB病毒基因组。在正常鼻咽黏膜的基底层以及55例NPC病例中的42例（76.4%）的细胞质中均观察到了Bcl-2。有丝分裂的肿瘤细胞通常显示出强烈的细胞质和染色体染色，这一发现此前未见详细报道。当采用仅包含两种主要显微镜类型的组织学分类时，Bcl-2表达与未分化NPC（UNPC）显著相关（p<0.05）。在EB病毒DNA的存在、NPC的位置、临床分期以及患者的年龄或性别与Bcl-2阳性表达之间，未发现密切相关性。然而，在比较Bcl-2表达与患者已知的平均生存期时，观察到了显著差异（p<0.001），因此，Bcl-2免疫反应性为 -、+、++和+++的NPC患者的平均生存期分别为31.1、24.4、52.2和54.1个月。然而，Bcl-2阳性的NPC病例中较好的临床结局可能取决于组织学类型，因为它与UNPC关系密切。只有通过对更大样本系列进行长期随访和多因素分析的研究，才能证明Bcl-2表达是否是NPC患者病情发展中的独立预后标志物。
