乳腺癌组织VEGF-C mRNA的表达对腋淋巴结阴性病人的预后价值

VEGF-C mRNA expression in breast cancer and its prognostic value in patients with negative axillary node

目的:探讨乳腺癌中VEGF-C mRNA的表达及其在腋淋巴结阴性病人中的预后价值。方法:将139例乳腺浸润性导管癌病人分为腋淋巴结阳性(axillary node positive,ANP)组(66例)和腋淋巴结阴性(axillary node negative,ANN)组(73例)。用原位杂交方法在组织芯片上检测VEGF-C mRNA表达;用免疫组化EnVision法检测广谱角蛋白(AE1/AE3)在腋淋巴结阴性(axillary node negative,ANN)组淋巴结中的表达,以判定微转移,结合随访结果判断其预后价值。结果:VEGF-C mRNA在腋淋巴结阳性(axillary node positive,ANP)组中的表达(53.0%)显著高于ANN组(27.4%)(P=0.001)。ANN组中,有14例病人腋窝淋巴结发现微转移灶,微转移率为19.2%(14/73);有微转移的病人其原发灶中VEGF-C mRNA表达率(50.0%)高于同组无微转移病人(22.4%),差别具有统计学意义(P=0.03)。ANN组中VEGF-C mRNA表达与肿块大小和组织学分级正相关,与ER、ki67和cerbB-2蛋白表达及病人年龄无关。经中位时间56个月的随访,ANN组中共有7人出现远处转移,均为VEGF-C mRNA表达者。结论:VEGF-C mRNA的表达与腋窝淋巴结转移相关;在ANN乳腺癌病人中VEGF-C mRNA的表达与淋巴结微转移密切相关;ANN乳腺癌病人癌组织中VEGF-C mRNA表达和淋巴结微转移提示其预后不佳。

Objective To detect VEGF-C mRNA expression in breast cancer and evaluate its prognostic value in patients with negative axillary node. Methods According to the status of axillary lymph nodes, 139 patients with infiltrative ductal breast cancer were divided into axillary node positive group （ANP group, n=66） and axillary node negative group （ANN group, n=73）. The clinical data of enrolled patients were reviewed. The expression of VEGF-C mRNA was detected by in situ hybridization（ISH）, and micrometastasis in axillary lymph nodes was additionally detected in ANN patients hy immunohistochemical staining of cytokeratin（AE1/AE3）. The expression of ER, cerbB-2 and Ki67 were also determined immunohistochemically. The prognostic value of VEGF-C mRNA and micremetastasis in axillary lymph nodes was evaluated based upon the outcome of patients in the follow-up. Results The expression of VEGF-C mRNA in the ANP group was significantly higher than that in ANN group （53.0% vs 27.4%, P=0.0011）. In the ANN group, micremetastasis in axillary lymph nodes was identified in14 patients （19.2% or 14/73）. A significant difference of VEGF-C mRNA expression was found between the micrometastasis positive sub-group and micremetastasis negative sub-group （50.0% vs 22.0%, P=0.0386）. VEGF-C mRNA expression was not correlated with age, the status of ER and cerbB-2 expression, as well as Ki67 expression, but was significantly correlated with tumor size and histological grading （P〈0.05）. After 56 months of follow-up, 7 patients in the ANN group but with VEGF-C mRNA expression developed distant metastases. Conclusions The expression of VEGF-C mRNA is correlated with axillary lymph node metastasis and micrometastasis in ANN breast cancer. Concomitant VEGF-C mRNA expression and micremetastasis in axillary lymh nodes indicate poor prognosis of ANN breast cancer patients.