乳腺癌外周血微转移与乳腺癌转移抑制基因1的相关性及临床意义

Clinical significance of peripheral blood metastasis and its relationship with BRMS1

目的探讨乳腺癌外周血微转移的临床意义及其与乳腺癌转移抑制基因1（breast cancer metastasis suppressor1，BRMSl）的相关性。方法应用RT-PCR技术检测149例浸润性乳腺癌术前外周血中微转移标志物hMAM—RNA的表达；免疫组化学方法检测术后乳腺癌组织中BRMSl蛋白的表达情况，术后随访其复发情况，SPSS19．0软件对相关数据进行统计分析。结果149例浸润性乳腺癌患者的术前外周血中有71例检测到微转移标志物hMAM—RNA的表达，微转移率为47．65％，且乳腺癌外周血微转移率与肿瘤TMN分期和是否有淋巴结转移及术后复发密切相关（P〈0．05），而与患者的年龄、肿瘤大小、病理类型和组织分型无关（P〉0．05）；BRMS1在术后的乳腺癌组织中有56例表达阳性，阳性率约37．58％，其中BRMSl阳性和阴性的乳腺癌病例中外周血出现微转移的病例分别为16例（阳性率为28．57％）和55例（阳性率为51．93％），两者差异有统计学意义，且呈明显负相关（r=-0．296，P〈0．01）；伴随着BRMS1蛋白染色阳性强度的逐渐增强，乳腺癌外周血微转移率呈现出明显下降的趋势（P〈0．05）；同时在外周血微转移阳性的患者中BRMS1阳性的患者的复发率（12．5％）显著低于BRMS1阴性的复发率（43．64％），两者差异有统计学意义（P〈0．05）。结论BRMS1的失表达与乳腺癌外周血微转移密切相关，BRMS1也可作为判定乳腺癌外周血微转移的一个重要的分子指标，常规检测乳腺癌组织中的BRMS1的表达有助于临床了解乳腺癌患者外周血微转移及术后复发的情况，从而指导临床个体化治疗和对预后的判定。

Objective To investigate the clinical significance of peripheral blood metastasis in breast cancer and its relationship with the metastasis suppressor gene BRMS1. Methods Reverse transcription poly- merase chain reaction （RT-PCR） was used to detect the expression of micrometastatic marker hlVIAM-RNA in the peripheral blood of 149 cases of invasive breast carcinoma. Immunohistochemical method was used to detect the expression of BRMS1 protein in breast cancer tissues after surgery. The recurrence was followed up. SPSS19.0 statistics software was used to analyze the data. Results Among the 149 cases of invasive breast carcinoma patients with preoperative peripheral blood, expression ot： hMAM-RNA was found in 71 cases, and the micrometastasis rate was 47.65%. Peripheral blood micrometastasis rate in breast cancer was closely related to tumor TMN stage, lymph node metastasis and postoperative recurrence（P〈0.05）; while it had nothing to do with patients＇ age, tumor size, pathological types or tumor tissue typing （P〉0.05）. The expression of BRMS1 in postoperative breast cancer tissue was detected in 56 cases, and the positive rate was 37.58%. For BRMS1 positive cases, 16 cases had peripheral blood micrometastasis （the positive rate was 28.57%）; For BRMS1 negative cases, 55 cases had peripheral blood micrometastasis （the positive rate was 51.93%）. The difference had statistical significance and the two showed a significant negative correlation（r=-0.296, P〈0.01 ）. With the gradual increase of positive staining intensity of BRMS1 protein, the micrometastasis rate of peripheral blood of breast cancer showed a significant decrease （P〈0.05）. At the same time, among patients with positive peripheral blood micrometastasis, the recurrence rate of patients with positive BRMS1 （12.5%） was significantly lower than that of patients with negative BRMSl（43.64%）, and the difference was statistically significant（P〈0.05）. Conclusions BRMS1 expression and breast cancer micrometastasis in peripheral blood is closely related. BRMS1 can also be used as an important molecular marker for determining micrometastasis in peripheral blood of breast cancer. Routine detection of BRMS1 expression in breast cancer tissue is helpful for clinical understanding of breast cancer patients, peripheral blood micrometastasis and postoperative recurrence, thus guiding clinical individualized treatment and prognosis.