胰腺癌淋巴管生成及其与生物学行为关系

Lymphangiogenesis in human pancreatic cancer and its relation with biological behaviors

目的研究胰腺癌淋巴管生成的机制、分布特征及其与胰腺癌临床病理学的关系。方法应用免疫组化双标记方法检测42例胰腺癌和12例癌旁胰腺组织中血管内皮生长因子-C(VEGF-C)及肾小球足突细胞黏蛋白(Podoplanin)的表达。结果42例胰腺癌组织VEGF-C阳性率为61.9%,12例癌旁胰腺组织中VEGF-C阳性表达率为58.3%,两者差异无显著性(χ2=0.050,P>0.05)。VEGF-C阳性率与胰腺癌的淋巴结转移有密切关系(χ2=4.822,P<0.05),而与胰腺癌大小、组织学分级、神经浸润及临床病理分期无关(P>0.05)。胰腺癌组织中可见明确的Podoplanin阳性淋巴管,其数目和分布具有明确的异质性。肿瘤边缘组织中淋巴管数最多,其次为肿瘤表浅部,而肿瘤中心区最少;在形态上,肿瘤边缘可以见到较多管腔扩张的淋巴管,而肿瘤中心及表浅淋巴管多为闭锁的条索状或点状。癌旁胰腺中Podoplanin阳性淋巴管分布在呈慢性炎症的胰腺组织周围,多数呈扩张状态。42例胰腺癌组织中LVD为7.67±1.25,12例癌旁胰腺组织中LVD为7.85±0.93,二者差别无显著性(t=0.639,P>0.05)。胰腺癌组织中LVD与淋巴结转移及临床病理分期有关(t=7.076,6.803,P<0.01),而与胰腺癌大小、组织学分级和神经浸润无关(P>0.05)。胰腺癌组织中VEGF-C的表达与LVD间呈正相关性(r=0.509,P<0.05)。结论胰腺癌及癌旁胰腺组织中VEGF-C高表达,促进淋巴管增生,可能是临床上胰腺癌早期发生淋巴结转移的重要机制之一。

Purpose To study the mechanism of lymphangiogenesis, its distributing character and relation with the clinicopathological features in human pancreatic cancer. Methods Immunohistochemical double staining was used to detect the expression of VEGF-C and podoplanin in 42 paraffin-embedded pancreatic carcinomas and 12 para-carcinomatous tissues. Results In 42 cases of pancreatic carci- noma, the positive rate of VEGF-C was 61.9%, and 58. 3% in 12 para-carcinomatous tissues, with no difference between them （ X^2 = 0. 050, P 〉 0. 05 ）. The expression of VEGF-C was closely correlated with lymph node metastasis （X^2 = 4. 822, P 〈 0. 05 ）, but not with tumor size, histological grade, nerve invasion and clinicopathological stages （P 〉 0. 05 ）. Clear podoplanin-positive lymphatic vessels were found in the pancreatic carcinoma, and the number and distribution had heterogeneity. The lymph vessels were predominantly located in the peri-tumor tissue, and next in the superficial area of the tumor, and intra-tumor were the least; The vast majority of the lymph vessels in the periphery of the tumor had wide open lumen, the intratumoral and superficial lymph vessels were collapsed. The para-carcinomatous tissues had chronic inflammation, and their podoplanin-positive lymphatic vessels had open lumen. In 42 cases of pancreatic carcinoma, the LVD was 7. 67 郭嫦媛 1.25, and that in 12 para-carcinomatous tissues was 7. 85 郭嫦媛0. 93. And there was no difference between them （t = 0. 639 ,P 〉 0. 05）. The LVD was closely correlated with lymph node metastasis and clinicopathological stages （t = 7. 076,6. 803, P 〈 0. 01 ）, but not with tumor size, histological grade and nerve invasion （P 〉 0. 05 ）. There was positive correlation between the expression of VEGF-C and LVD （ r = 0. 509,P 〈 0. 05 ）. Conclusions The overexpression of VEGF-C protein in the pancreatic carcinoma and para-carcinomatous tissues promotes lymphangiogenesis in the tumor. It may be the important mechanism that induces the lymph node metastasis of pancreatic cancer early.