胰腺癌组织中微血管密度和淋巴管密度对术后1年内肿瘤远处转移的预测价值

Predictive value of microvessel density and lymphatic vessel density in pancreatic cancer tissue for tumor distant metastasis within 1 year after surgery

目的探讨胰腺癌组织中的微血管密度(MVD)和淋巴管密度(LVD)对患者肿瘤术后1年内远处转移的预测价值。方法回顾性分析2020年1月至2021年12月间广西来宾市人民医院收治的47例胰腺癌手术患者的临床病理资料,根据术后1年随访期间内是否发生肿瘤远处转移分为无转移组(24例)和转移组(23例)。采用免疫组织化学方法检测胰腺癌组织微血管上皮细胞CD34及淋巴管上皮细胞D2-40的表达,计数癌组织和癌旁正常组织中MVD、LVD,分析癌组织MVD、LVD与患者性别、年龄、肿瘤长径、肿瘤分化程度、淋巴结转移、脉管侵犯、神经侵犯、肿瘤分期等临床病理特征的关系。绘制受试者工作特征曲线(ROC),计算曲线下面积(AUC),评估癌组织MVD、LVD预测胰腺癌术后肿瘤1年内远处转移的价值。分析MVD、LVD对胰腺癌术后1年内肿瘤远处转移率的影响。采用单因素和多因素logistic回归分析胰腺癌术后1年内肿瘤远处转移的独立影响因素。结果转移组癌组织中MVD和LVD高于癌旁正常组织[(72.52±9.73)个/400倍视野比(51.73±7.95)个/400倍视野、(23.78±6.87)个/400倍视野比(14.00±5.66)个/400倍视野],无转移组癌组织中MVD和LVD也高于癌旁正常组织[(63.20±6.52)个/400倍视野比(54.79±5.80)个/400倍视野、(16.25±5.15)个/400倍视野比(13.62±5.03)个/400倍视野],差异均有统计学意义(P<0.05)。肿瘤长径≥2 cm、淋巴结转移、脉管侵犯、TNM高分期患者的癌组织MVD显著增高(P<0.05),肿瘤长径≥2 cm、肿瘤中低分化、淋巴结转移、脉管侵犯、神经侵犯、TNM高分期患者的癌组织LVD显著增高(P<0.05)。癌组织中MVD和LVD预测胰腺癌术后1年内肿瘤远处转移的AUC值分别为0.799(95%CI0.659~0.939)、0.803(95%CI0.676~0.929),预测临界值(Cut-off值)分别为70.5、20.5个/400倍视野,灵敏度分别为73.9%、69.6%,特异度分别为87.5%、83.7%。高MVD值和高LVD组术后1年内累积肿瘤远处转移率显著高于低MVD组和低LVD组(P值均<0.05)。多因素logistic回归分析显示,肿瘤长径≥2 cm(OR=1.757,95%CI1.536~3.846,P<0.05)、淋巴结转移(OR=2.364,95%CI1.036~4.175,P<0.05)、高MVD(OR=4.345,95%CI1.245~3.736,P<0.05)和高LVD(OR=3.637,95%CI1.426~4.035,P<0.05)是胰腺癌术后1年内肿瘤远处转移的独立危险因素。结论胰腺癌组织中MVD和LVD增高,是术后肿瘤1年内远处转移的独立影响因素,可用于预测患者术后1年内有无肿瘤远处转移。

Objective To investigate the value of counting microvessel density(MVD)and lymphatic vessel density(LVD)in predicting distant metastasis of pancreatic cancer within 1 year after surgery.Methods The clinicopathological data of 47 patients with pancreatic cancer who underwent surgery in Laibin People's Hospital from January 2020 to December 2021 were retrospectively analyzed.The patients were divided into non-metastasis group(n=24)and metastasis group(n=23)according to whether distant metastasis occurred during 1-year follow-up.Immunohistochemistry was used to detect the CD34 expression in microvascular epithelial cells and D2-40 level in lymphatic epithelial cells from pancreatic cancer tissues.MVD and LVD in cancer tissues and adjacent normal tissues were counted.The relationship between MVD and LVD in cancer tissues and clinicopathological characteristics such as gender,age,tumor diameter,tumor differentiation,lymph node metastasis,vascular invasion,nerve invasion and tumor stage were analyzed.The receiver operating characteristic curve(ROC)was drawn and the area under the curve(AUC)was calculated to evaluate the value of MVD and LVD in predicting distant metastasis of pancreatic cancer within 1 year after surgery.The effects of MVD and LVD on the distant metastasis rate of pancreatic cancer within one year after operation were evaluated.Univariate and multivariate logistic regression were used to analyze the independent influencing factors for distant metastasis of pancreatic cancer within 1 year after surgery.Results MVD and LVD in metastatic cancer tissues were higher than those in adjacent normal tissues[(72.52±9.73)vs(51.73±7.95)/400 times field of view,(23.78±6.87)vs(14.00±5.66)/400 times field of view].MVD and LVD in the non-metastasis group were also higher than those in the adjacent normal tissues[(63.20±6.52)vs(54.79±5.80)/400 times field of view,(16.25±5.15)vs(13.62±5.03)/400 times field of view],and all the differences were statistically significant(P<0.05).MVD in cancer tissue was significantly increased in patients with tumor diameter≥2 cm,lymph node metastasis,vascular invasion and high TNM stage(P<0.05),and LVD was significantly increased in patients with tumor diameter≥2 cm,lymph node metastasis,moderate and low differentiation,vascular invasion,nerve invasion and high TNM stage(P<0.05).The AUC values of MVD and LVD in predicting distant metastasis of pancreatic cancer within 1 year after surgery were 0.799(95%CI 0.659-0.939)and 0.803(95%CI 0.676-0.929),and the cut-off values were 70.5 and 20.5/400 times field of view,respectively.The sensitivity was 73.9%and 69.6%,and the specificity was 87.5%and 83.7%.The cumulative distant metastasis rate within 1 year after operation in high MVD and high LVD groups was significantly higher than that in low MVD and low LVD groups(P<0.05).Multivariate logitic regression analysis showed that tumor diameter≥2 cm(OR=1.757,95%CI 1.536-3.846,P<0.05),lymph node metastasis(OR=2.364,95%CI 1.036-4.175,P<0.05),high MVD(OR=4.345,95%CI 1.245-3.736,P<0.05)and high LVD(OR=3.637,95%CI 1.426-4.035,P<0.05)were independent risk factors for distant metastasis of pancreatic cancer within 1 year after surgery.Conclusions Increased MVD and LVD in pancreatic cancer tissues are independent influencing factors for distant metastasis within 1 year after surgery,which can be used to predict whether patients have distant metastasis within 1 year after surgery.