Clinical significance of vascular endothelial growth factor-C and vascular endothelial growth factor receptor 3 in patients with T1 lung adenocarcinoma
Clinical significance of vascular endothelial growth factor-C and vascular endothelial growth factor receptor 3 in patients with T1 lung adenocarcinoma
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作者：
Kojima, H;Shijubo, N;Sato, N
背景血管内皮生长因子-C（VEGF-C）在淋巴管生成中起重要作用，并激活VEGF受体-3（VEGFR-3）。淋巴结转移是影响肺腺癌患者预后的重要因素。本研究旨在探讨TNM分期为T1的肺腺癌中VEGF-C和VEGFR-3的表达与临床病理因素及预后的关系。作者对129例接受T1肺腺癌完全切除术的连续患者进行了回顾性分析。对VEGF-C、VEGF、VEGFR-3、CD 34（微血管）、类胰蛋白酶（肥大细胞）和CD 68（巨噬细胞）进行免疫组织化学染色，以统计学分析VEGF-C和VEGFR-3状态的临床病理学意义。在129例T1肺腺癌患者中，56例（43.3%）患者肿瘤细胞VEGF-C阳性，73例（56.6%）患者肿瘤细胞和内皮细胞VEGFR-3阳性，分别为69例（53.5%）。肿瘤细胞VEGF-C阳性表达的患者的生存率明显低于阴性表达的患者（P = 0.031）。肿瘤细胞和内皮细胞VEGFR-3阳性表达者的生存率均显著低于阴性表达者（P = 0.0034和P = 0.0020）。肿瘤细胞VEGF-C和内皮细胞VEGFR-3均阳性的患者表现出最不利的预后。多因素分析显示，肿瘤细胞VEGF-C和内皮细胞VEGFR-3共表达是独立的负性预后因素（P = 0.0129），N因素（P = 0.0020）也是独立的负性预后因素。VEGF-C和VEGFR-3状态可能是T1肺腺癌患者生存率的指标。
BACKGROUND. Vascular endothelial growth factor-C (VEGF-C) plays an important role in lymphangiogenesis and activates VEGF receptor-3 (VEGFR-3). Lymphatic spread is an important prognostic factor in patients with lung adenocarcinoma. The aim of the current study was to determine whether the expression of VEGF-C and VEGFR-3 correlates with clinicopathologic factors and prognosis in patients with TNM classification T1 lung adenocarcinoma.METHODS. The authors conducted a retrospective review of 129 consecutive patients who underwent complete resection for T1 lung adenocarcinoma. Immuno- histochernical staining for VEGF-C, VEGF, VEGFR-3, CD34 (microvessels), tryptase (mast cells), and CD68 (macrophages) was performed to statistically analyze clin- icopathologic implications of VEGF-C and VEGFR-3 status.RESULTS. Of 129 patients with T1 lung adenocarcinoma, 56 (43.3%) patients were positive for tumor-cell VEGF-C and 73 (56.6%) and 69 (53.5%) patients were positive for tumor-cell and endothelial-cell VEGFR-3, respectively. Patients with positive staining for tumor-cell VEGF-C showed significantly less favorable survival rates than patients with negative staining (P = 0.031). The survival rates of patients with positive staining for tumor-cell and endothelial-cell VEGFR-3 were significantly cantly lower than those with negative staining (P = 0.0034 and P = 0.0020, respectively). Patients with positive staining for both tumor-cell VEGF-C and endothelial-cell VEGFR-3 exhibited the most unfavorable prognoses. Multivariate analysis demonstrated that coexpression of tumor-cell VEGF-C and endothelialcell VEGFR-3 was an independent negative prognostic factor (P = 0.0129) as well as N factor (P = 0.0020).CONCLUSIONS. VEGF-C and VEGFR-3 status may be indicative of survival rates for patients with T1 lung adenocarcinoma.