腋淋巴结阴性乳腺癌外周血hMAM检测意义

目的:应用乳腺癌特异性标志物乳腺珠蛋白(hMAM)检测腋淋巴结阴性乳腺癌(axillary lymph node negative breast cancer,ALNNBC)外周血中微转移,并探讨其与临床病理因素的关系.方法:采用巢式RT-PCR方法,分别检测62例ALNNBC、6例乳腺良性疾患和6例健康成人女性外周血中hMAM mRNA的表达,并以MDA-MB415细胞为阳性参考检测该方法的灵敏度.结果:ALNNBC外周血hMAM表达阳性率为32.3%(20/62),乳腺良性疾患组和健康成人女性组全部阴性表达;该方法检测外周血微转移的灵敏度达1/106;C-erbB2基因阳性表达者微转移发生率高(P＜0.01),月经状态、肿瘤大小、组织学类型、ER状态、p53表达等与微转移无关(P＞0.05);复发转移组较无瘤生存组外周血中微转移率高(P＜0.01).结论:hMAM可作为乳腺癌外周血微转移的标志物;ALNNBC微转移与C-erbB2密切相关;外周血微转移可以作为ALNNBC预后指标.

The Detection of hMAM in Peripheral Blood and the Clinical Significance in Axillary Lymph Node Negative Breast Cancer Patients

Objective: To determine micrometastasis in peripheral blood of axillary lymph node negative breast cancer(ALNNBC) patients with a new specific breast cancer marker and to discuss the relations between micrometastasis and some clinical and pathological factors and prognosis. Methods: Blood samples were obtained from 62 patients with ALNNBC, of which 6 patients with breast benign disease and 6 healthy adult women were screened for human mammaglobin(hMAM) mRNA by a nested RT-PCR assay. The sensitivity was assessed by detecting MDA-MB415 cells in healthy peripheral blood at different concentrations. Results: The assay exhibited a calculated analytical limit of one tumor cell per 106 mononucleus cells. None of the samples from the patients with breast benign disease and the healthy adult women was positive, whereas 20 (32.3%) of 62 samples from patients with ALNNBC were positive for hMAM mRNA. It was also found that the micrometastasis rate was rather high in the C-erbB2-positive group (P<0.01) while it didn't correlate with menopausal status, tumor size, histological type, ER status and p53. It was significantly discovered that the micrometastasis rate in the metastatic group was apparently higher than in free-disease survival group (P<0.01). Conclusions: hMAM is at present one of the most sensitive and specific marker for detecting micrometastasis in peripheral blood of breast cancer. Micrometastasis of ALNNBC has a close, relationship with C-erbB2 and might be a predictor of prognosis.