Dhar Dipok Kumar, Ono Takashi, Yamanoi Akira, Soda Yukiko, Yamaguchi Emi, Rahman Md Atikur, Kohno Hitoshi, Nagasue Naofumi
Second Department of Surgery, Shimane Medical University, Izumo, Japan.
Cancer. 2002 Nov 15;95(10):2188-95. doi: 10.1002/cncr.10972.
Tumor angiogenesis is a strong prognostic factor in patients with hepatocellular carcinoma (HCC). However, to the authors' knowledge, details regarding the serum levels of proangiogenic and antiangiogenic growth factors controlling this process are not yet known.
Serum endostatin, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) levels were measured by the enzyme immunoassay method in prospectively collected samples from 33 HCC patients who had received no preoperative therapy. The angiogenic score (AS) and endostatin localization were evaluated using immunohistochemistry.
Significant decreases in serum endostatin (P = 0.0007) and bFGF (P = 0.0004) were observed in postoperative samples compared with the preoperative values. A very strong direct correlation was noted between VEGF and endostatin (P < 0.0001). Only the preoperative serum endostatin was found to have a significant (P = 0.0025) inverse correlation with the AS. Furthermore, the combined positivity for bFGF and VEGF and negativity for endostatin was found to have a significantly (P = 0.0069) positive correlation with AS. Significantly high levels of endostatin were noted in patients with trabecular-type tumors (P = 0.0446) and in patients with hepatitis B infection (P = 0.0183). The serum endostatin level was found to be significantly (P = 0.0166) higher in living patients and patients with high serum endostatin levels had a tendency (P = 0.0871) toward long survival. Tissue endostatin expression was found to have a direct correlation with the serum endostatin level (P = 0.0117).
The measurement of serum endostatin can predict tumor vascularity and may serve as a promising tool in the antiangiogenic therapy for patients with HCC.
肿瘤血管生成是肝细胞癌(HCC)患者的一个重要预后因素。然而,据作者所知,关于控制这一过程的促血管生成和抗血管生成生长因子的血清水平的详细情况尚不清楚。
采用酶免疫分析法,对33例未接受术前治疗的HCC患者前瞻性采集的样本进行血清内皮抑素、血管内皮生长因子(VEGF)和碱性成纤维细胞生长因子(bFGF)水平检测。采用免疫组织化学方法评估血管生成评分(AS)和内皮抑素定位。
与术前值相比,术后样本中血清内皮抑素(P = 0.0007)和bFGF(P = 0.0004)显著降低。VEGF与内皮抑素之间存在非常强的直接相关性(P < 0.0001)。仅术前血清内皮抑素与AS呈显著负相关(P = 0.0025)。此外,发现bFGF和VEGF的联合阳性以及内皮抑素的阴性与AS呈显著正相关(P = 0.0069)。小梁型肿瘤患者(P = 0.0446)和乙型肝炎感染患者(P = 0.0183)的内皮抑素水平显著升高。发现存活患者的血清内皮抑素水平显著更高(P = 0.0166),血清内皮抑素水平高的患者有长期生存的趋势(P = 0.0871)。发现组织内皮抑素表达与血清内皮抑素水平直接相关(P = 0.0117)。
血清内皮抑素的检测可预测肿瘤血管生成,可能成为HCC患者抗血管生成治疗的一个有前景的工具。