Fondevila C, Metges J P, Fuster J, Grau J J, Palacín A, Castells A, Volant A, Pera M
Services of Gastrointestinal Surgery, Institut de Malalties Digestives, Hospital Clínic, Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), University of Barcelona Medical School, Barcelona, Spain.
Br J Cancer. 2004 Jan 12;90(1):206-15. doi: 10.1038/sj.bjc.6601455.
This study was undertaken to determine the value of tumour microvessel density (MVD) and the expression of p53 and vascular endothelial growth factor (VEGF) as prognostic markers in patients with gastric cancer operated on for cure. In all, 156 patients with curatively resected gastric cancer constituted the basis of this blinded retrospective evaluation. Patients were treated with either surgery alone (n=53) or surgery plus adjuvant chemotherapy (n=103). Tumour MVD, p53 expression, and VEGF expression were assayed using immunohistochemical techniques. After a mean follow-up of 43 months, 64 (41%) patients had died and 55 (35%) patients developed tumour recurrence. Positive correlations between MVD and both p53 (P=0.005) and VEGF (P=0.005) expression were observed. Both MVD >/=100 (P=0.05) and positive VEGF expression (P<0.02) were associated with shorter disease-free survival, and positive VEGF expression (P=0.01) was also associated with shorter overall survival. Multivariate analysis confirmed that, in addition to the pathological tumour stage, lymph node ratio, the extent of lymphadenectomy and perineural invasion, p53 expression, and VEGF expression were independently associated with both disease-free survival (P<0.0005 and 0.02, respectively) and overall survival (P<0.02 and 0.01, respectively). Finally, patients whose tumours did not show p53 expression had a survival benefit compared to those expressing p53 when treated with adjuvant chemotherapy (P=0.01). This investigation demonstrates that p53 expression and VEGF expression are independent prognostic factors for both disease-free survival and overall survival in patients with curatively resected gastric cancer, and that p53 status may also influence response to chemotherapy.
本研究旨在确定肿瘤微血管密度（MVD）以及p53和血管内皮生长因子（VEGF）的表达作为接受根治性手术的胃癌患者预后标志物的价值。总共156例接受根治性切除的胃癌患者构成了这项盲法回顾性评估的基础。患者接受单纯手术治疗（n = 53）或手术加辅助化疗（n = 103）。使用免疫组织化学技术检测肿瘤MVD、p53表达和VEGF表达。平均随访43个月后，64例（41%）患者死亡，55例（35%）患者出现肿瘤复发。观察到MVD与p53（P = 0.005）和VEGF（P = 0.005）表达均呈正相关。MVD≥100（P = 0.05）和VEGF阳性表达（P<0.02）均与无病生存期缩短相关，VEGF阳性表达（P = 0.01）也与总生存期缩短相关。多变量分析证实，除了病理肿瘤分期、淋巴结比率、淋巴结清扫范围和神经周围浸润外，p53表达和VEGF表达分别与无病生存期（P<0.0005和0.02）和总生存期（P<0.02和0.01）独立相关。最后，与接受辅助化疗时表达p53的患者相比，肿瘤未显示p53表达的患者具有生存获益（P = 0.01）。这项研究表明，p53表达和VEGF表达是根治性切除胃癌患者无病生存期和总生存期的独立预后因素，并且p53状态也可能影响化疗反应。
