【作者】 颜歌； 周晓燕； 张瑰红； 杜祥；

【Author】 Yan Ge Zhou Xiao-Yan Zhang Gui-Hong Du Xiang Department of Pathology, Cancer Hospital of Fudan University, Department of Oncology, Shanghai Medical College, Fudan University, Colorectal Cancer Center, Fudan University,Shanghai 200032,China

【机构】 复旦大学附属肿瘤医院病理科复旦大学上海医学院肿瘤学系复旦大学大肠癌诊治中心；

【摘要】 目的:淋巴道、血道是恶性肿瘤尤其是癌发生转移的主要途径。随着淋巴管标记物的不断发展和更新,淋巴管生成在肿瘤及转移中的作用日益成为热点问题。结直肠癌局部淋巴结转移十分常见,但其淋巴管生成与转移的关系目前仍不清楚。D2—40是一种新近发现的淋巴管特异性标记物。本研究拟观察结直肠癌组织淋巴管生成和血管生成的情况, 探讨淋巴管生成、血管生成与肿瘤转移的关系,并验证D2— 40标记淋巴管的特异性。方法:分别采用新的淋巴管特异性标记物D2—40和FⅧ相关抗原对132例散发性结直肠癌(其中转移组74例,未转移组58例)进行免疫组织化学染色检测微淋巴管密度(lymphatic vessel density,LVD)和微血管密度(microvessel density,MVD),分析二者在结直肠癌转移过程中的意义,同时进行双标免疫组织化学染色,观察D2—40的特异性。结果:结直肠癌组织内部新生淋巴管、血管较稀疏,常呈点状或挤压成裂隙状,癌周边与正常组织交界处淋巴管、血管较密集,管腔不规则,有时扩张呈囊状。转移组结直肠癌组织的LVD值(12．08±4．96)明显高于未转移组的结直肠癌(8．26±4．08)(P<0．001),转移组结直肠癌组织的MVD值(23．74±12．02)明显高于未转移组的结直肠癌(18．16±9．42)(P<0．01)。IND对于预测结直肠癌有无转移的特异性为71．62％,敏感度为56．90％,对应此特异性和敏感度的LVD值为5,LVD每增加1,结直肠癌患者发生转移的风险将增加1．45倍。MVD对于预测结直肠癌有无转移的特异性为66．22％,敏感度为51．72％,MVD每增加1,结直肠癌患者发生转移的风险将增加1．11倍。免疫组化双标显示D2—40标记的淋巴管与FⅧ相关抗原标记的血管特异性好,两者几无交叉反应。结论:癌周LVD和MVD增加与癌细胞转移相关,且LVD的特异性和敏感度较MVD高, 对二者进行测定可能对于结直肠癌疾病进展评估及预测肿瘤转移和预后具有重要价值。D2—40是一种特异性较好的淋巴管标记物。更多还原

【Abstract】 Objective: Lymphatic vessels and microvessles are main paths for malignant tumor metastasis, especially for cancer. More and more researchers focus on the importance of lymphogenesis in tumorigenesis and metastasis because of the development and update of new markers for lymphatic vessels. It is a common phenomenon that metastatic local lymph node in sporadic colorectal carcinoma (SCRC), but the relationship between the lymphogenesis and metastasis is not clear. D2-40, a recently available monoclonal antibody that has been used as a lymphatic endothelial marker. Our aim is to investigate the distribution pattern of lymphatic vessels and microvessles in SCRC and their relationship with tumor metastasis and disease prognosis and to validate the specificity of D2-40 as a lymphatic endotheiial marker. Methods: The lymphatic vessel density (LVD) and microvessel denisity (MVD) in tumoral areas of 132 cases of primary SCRC, including 74 metastatic cases and 58 non-metastatic cases, were evaluated by immunohistochemistry, using monoclonal antibodies for D2-40 and F VIII related antigen respectively. At the same time, we detected them by double labeling immunohistochemistry. Results: The lymphatic vessels and microvessels at central portions of SCRC often had a reticular architecture with numerous tiny and ill-defined lumina, while those at the tumor borders had large and open lumina. The LVD was obviously higher in the cases of colorectal carcinoma with metastasis (12.08 ± 4.96) than in the cases without metastasis (8.26 ± 4.08) (p<0.001),the MVD was obviously higher in the cases of colorectal carcinoma with metastasis (23.74 ± 12.02) than in the cases without metastasis (18.16 ± 9.42) (p<0.01). The specificity and sensitivity of LVD in predicting metastasis or non-metastasis in SCRC were 71.62% and 56.90%, and the corresponding LVD was 5. For each one lymphatic vessel increased, there was a 1.45-fold increase in the risk of metastasis in SCRC. The specificity and sensitivity of MVD were 66.22% and 51.72%, respectively. For each one microvessel increased, there was a 1.11-fold increase in the risk of metastasis in SCRC. The results of double labeling immunohistochemistry showed it is specific for D2-40 to be as a lymphatic endothelial marker. There is no cross-reaction between the D2-40 and F VIII related antigen. Conclusion: Lymphogenesis and angiogen-esis are commonly seen in SCRC, especially at tumor borders. High LVD and MVD at tumor borders are associated with metastasis, especially the LVD. The specificity and sensitivity of LVD are higher than that of MVD. The detection of LVD and MVD at tumor borders may thus be useful in predicting metastasis and prognosis in patients with SCPC. D2-40 was a specific and sensitive marker for lymphatic endothelial marker.更多还原