Theodoropoulos George E, Karafoka Eleni, Papailiou Joanna G, Stamopoulos Paraskevas, Zambirinis Constantinos P, Bramis Konstantinos, Panoussopoulos Sotirios-George, Leandros Emmanouil, Bramis John
First Propaedeutic Surgical Department, Hippocration Hospital, School of Medicine, University of Athens, Athens, Greece.
Anticancer Res. 2009 Feb;29(2):785-91.
Extensive research into the biology of colorectal cancer has identified a plethora of molecular markers reputed to provide prognostic information. During the last two decades conflicting results have been drawn on the role of the p53 tumour suppressor gene and of the first identified member of the type receptor tyrosine kinase family, EGFR, on colorectal cancer prognosis, p53 Mutational status has been associated with both improved and reduced survival. EGFR has been associated with reduced length of survival, increasing Dukes' stage and lymph node metastases in several reports, but as many studies have reported no association with unfavourable prognostic parameters. The aim of this study was to evaluate the p53 and EGFR expression in patients with an at least 5-year follow-up.
Paraffin-embedded material was retrospectively collected from 164 colorectal adenocarcinoma (50 rectal) patients, who had been operated on between 1994 and 2003. The median follow-up was 5 years (range: 1-14). p53 and EGFR expression were evaluated by immunohistochemistry.
Positive p53 immunostaining and EGFR expression was observed in 63.4% and 43.9% of patients, respectively. p53 and EGFR positivity rates were significantly interrelated (p = 0.004). No significant correlation was found with the examined clinicopathological parameters except for advanced T-stage, which demonstrated significant associations with p53 expression (p = 0.004), EGFR expression (p = 0.0001) and p53/EGFR coexpression (p = 0.001). In univariate survival analysis (log rank test), stage (p = 0.0001), lymphovascular invasion (p = 0.005) and perineural infiltration (p = 0.004) were associated with the overall cancer-specific survival, while a trend existed for EGFR (p = 0.06) and p53/EGFR coexpression (p = 0.07). On multivariate analysis, only stage was associated with increased risk of cancer death (Cox regression analysis p = 0.0001, b-coefficient (SE): 1.898 (0.383).
p53 and EGFR were overexpressed in this colorectal cancer patient population and were significantly associated with advanced T stage. In the context of new therapeutic strategies using EGFR-targeted therapies, although EGFR remains a controversial prognostic factor, this expression-stage association may play a crucial role in a decision to initiate an adjuvant treatment.
对结直肠癌生物学的广泛研究已确定了大量据称可提供预后信息的分子标志物。在过去二十年中，关于p53肿瘤抑制基因以及首个被鉴定的受体酪氨酸激酶家族成员EGFR在结直肠癌预后中的作用得出了相互矛盾的结果。p53突变状态与生存率的提高和降低均有关联。在一些报告中，EGFR与生存期缩短、Dukes分期增加和淋巴结转移相关，但也有许多研究报告称其与不良预后参数无关联。本研究的目的是评估至少随访5年的患者中p53和EGFR的表达情况。
回顾性收集了1994年至2003年间接受手术的164例结直肠腺癌（50例为直肠癌）患者的石蜡包埋材料。中位随访时间为5年（范围：1 - 14年）。通过免疫组织化学评估p53和EGFR的表达。
分别在63.4%和43.9%的患者中观察到p53免疫染色阳性和EGFR表达阳性。p53和EGFR阳性率显著相关（p = 0.004）。除了进展期T分期外，未发现与所检查的临床病理参数有显著相关性，进展期T分期与p53表达（p = 0.004）、EGFR表达（p = 0.0001）以及p53/EGFR共表达（p = 0.001）均显示出显著关联。在单因素生存分析（对数秩检验）中，分期（p = 0.0001）、淋巴管浸润（p = 0.005）和神经周围浸润（p = 0.004）与总体癌症特异性生存相关，而EGFR（p = 0.06）和p53/EGFR共表达（p = 0.07）存在相关趋势。在多因素分析中，只有分期与癌症死亡风险增加相关（Cox回归分析p = 0.0001，b系数（标准误）：1.898（0.383））。
在该结直肠癌患者群体中，p53和EGFR过度表达，且与进展期T分期显著相关。在使用EGFR靶向治疗的新治疗策略背景下，尽管EGFR仍然是一个有争议的预后因素，但这种表达与分期的关联可能在决定启动辅助治疗中起关键作用。
