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[结直肠癌患者淋巴管、淋巴管密度及血管内皮生长因子-C检测的临床意义]

[Clinical significance of detection on lymphatic microvessel, lymphatic microvessel density and vascular endothelial growth factor-C in patients with colorectal carcinoma].

作者信息

Fan Yue-zu, Li Guang-ming, Huang Guo-ping, Li Xin-ping

机构信息

Department of Surgery, Tongji Hospital, Shanghai Tongji University, Shanghai 200065, China.

出版信息

Zhonghua Wei Chang Wai Ke Za Zhi. 2006 Nov;9(6):477-82.

Abstract

OBJECTIVE

To evaluate the clinical significance of detection on lymphatic microvessel, lymphatic microvessel density (LMVD) and vascular endothelial growth factor-C (VEGF-C) in patients with colorectal carcinoma.

METHODS

Eighty tissue specimens of the colorectal carcinoma and the peritumoral tissue and thirty of adjacent normal bowel tissue were collected. The lymphatic microvessel and LMVD were determined by 5'-nucleotidase histochemical staining. The expression of VEGF-C protein and VEGF-C mRNA in specimens of colorectal carcinoma and normal colorectal tissues were studied by RT-PCR and immunohistochemical methods utilizing strept-avidin-biotin complex. Clinicopathological data and survival of each patient were obtained and analyzed.

RESULTS

(1) The brown or filemot stained lymphatic microvessels were observed in specimens from the colorectal carcinoma, the peritumoral tissue and the normal bowel. Collapsed, nonfunctional lymphatic vessels were observed in the intratumoral tissue, and plenty of lymphatic vessels with large lumen referred as functional lymphatic vessels were observed in the peritumoral tissue. (2) The mean value of LMVD in the peritumoral tissue was significantly higher than that in the normal bowel tissue (9.76+/-2.85 vs. 5.49+/-1.43, t=8.220, P<0.01) and tumor tissue (9.76+/-2.85 vs. 2.13+/-0.96, t=15.118, P<0.001). (3) The positive rate (48.8% vs. 0, P<0.01) and mean value (1.09+/-1.20 vs. 0, P<0.01) of the VEGF-C protein expression in colorectal carcinoma specimens were significantly higher than that of the normal bowel tissue. The expression of VEGF-C protein was consistent with the expression of VEGF-C mRNA. The VEGF-C expression in intratumoral tissue demonstrated significant correlation with LMVD in the peritumoral tissue of colorectal carcinoma. (4) Both LMVD in the peritumoral tissue and the expression of VEGF-C in the intratumoral tissue correlated significantly with Dukes' stage (P<0.0001 and P=0.0234), lymph node metastasis (P<0.0001 and P=0.0059), and survival (P<0.0001 and P<0.0001), but not with age, sex, location and dimension of lesion, gross and histological type. Also, there was a positive significant correlation of LMVD in the peritumoral tissue with degree of differentiation (P=0.0168) and metastasis to the liver or the lung (P=0.0088).

CONCLUSIONS

Lymphatic microvessels in the peritumoral tissue are functional. The functional lymphatic microvessels, increased LMVD in the peritumoral tissue and the expression of VEGF-C in the intratumoral tissue may act as the morphological features and the molecular phenotype of lymphangiogenesis in colorectal carcinoma, and also as important predictive markers for evaluating lymphatic metastasis and prognosis in patients with colorectal carcinoma.

摘要

目的

评估检测结直肠癌患者淋巴管、淋巴管微密度(LMVD)及血管内皮生长因子-C(VEGF-C)的临床意义。

方法

收集80例结直肠癌组织标本、癌旁组织标本及30例相邻正常肠组织标本。采用5'-核苷酸酶组织化学染色法测定淋巴管及LMVD。运用链霉亲和素-生物素复合物的逆转录聚合酶链反应(RT-PCR)和免疫组织化学方法,研究结直肠癌标本及正常结直肠组织中VEGF-C蛋白和VEGF-C mRNA的表达。获取并分析每位患者的临床病理资料及生存情况。

结果

(1)在结直肠癌、癌旁组织及正常肠组织标本中均观察到棕色或黄褐色染色的淋巴管。肿瘤组织内可见塌陷、无功能的淋巴管,而癌旁组织中可见大量管腔较大的功能性淋巴管。(2)癌旁组织中LMVD的平均值显著高于正常肠组织(9.76±2.85对5.49±1.43,t = 8.220,P < 0.01)及肿瘤组织(9.76±2.85对2.13±0.96,t = 15.118,P < 0.001)。(3)结直肠癌标本中VEGF-C蛋白表达的阳性率(48.8%对0,P < 0.01)及平均值(1.09±1.20对0,P < 0.01)显著高于正常肠组织。VEGF-C蛋白表达与VEGF-C mRNA表达一致。结直肠癌肿瘤组织内VEGF-C表达与癌旁组织中LMVD呈显著相关。(4)癌旁组织中LMVD及肿瘤组织中VEGF-C表达均与Dukes分期(P < 0.0001和P = 0.0234)、淋巴结转移(P < 0.0001和P = 0.0059)及生存情况(P < 0.0001和P < 0.0001)显著相关,但与年龄、性别、病变部位及大小、大体及组织学类型无关。此外,癌旁组织中LMVD与分化程度(P = 0.0168)及肝或肺转移(P = 0.0088)呈显著正相关。

结论

癌旁组织中的淋巴管具有功能。功能性淋巴管、癌旁组织中增加的LMVD及肿瘤组织中VEGF-C的表达可能是结直肠癌淋巴管生成的形态学特征和分子表型,也是评估结直肠癌患者淋巴转移及预后的重要预测指标。

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