Abstract: Objective: To explore the positive expressions of biological markers human mammaglobin(hMAM)combined with matrix metallopeptidase 9(MMP-9) and human epidermal growth factor receptor 2(C-erbB2)mRNA in peripheral blood of the breast cancer patients with micrometastases,and to clarify its clinical application value in diagnosis of the micrometastases in peripheral blood of the breast cancer patients. Methods: A total of 74 patients with breast cancer,21 patients with breast fibroadenoma and 10 healthy controls were selected as the subjects. All the patients received surgical treatment and the peripheral blood was collected.The mRNA expression levels of hMAM,MMP-9 and C-erbB2 in peripheral blood were measured by the real-time fluorescent quantitative PCR.The positive expression rates of detection of hMAM,MMP-9 and C-erbB2 were compared,and the differences in detection of hMAM combined with MMP-9 and C-erbB2 between the patients with different clinicopathologic features were analyzed. Results: In the breast cancer patients with lymph node metastasis,the differences of positive expression rates ofMMP-9 and C-erbB2 mRNA were significant(χ²=6.450, P<0.05;χ²=5.636, P<0.05),and the difference of positive expression rate of hMAM mRNA was sigificant between HER-2 positive and negative patients(χ²=5.804, P<0.05).The positive expression rates ofindividualhMAM and combined with MMP-9 and C-erbB2 were 37.84%(28/74),59.46%(44/74)and 48.65%(36/74)in the breast cancer patients,the combined postive expression rate of these three kinds of markers was 64.86%(48/74),which were higher than those in healthy controls group(χ²=5.676,P<0.05;χ²=3.102,P>0.05;χ²=5.339,P<0.05;χ²=2.310,P>0.05),fibroadenoma ofbreast group(χ²=8.438, P<0.01; χ²=4.491, P<0.05; χ²=7.982, P<0.01; χ²=4.844, P<0.05)and non-breast cancer group(healthy controls group+ breast fibroadenoma group)(χ²=13.093, P<0.01; χ²=6.471, P<0.05; χ²=11.837, P<0.01;χ²=6.103, P<0.05).The positive expression rates ofindividualhMAM and the joint detection in the breast cancer patients at stage Ⅲ+Ⅳ were higher than those in the patients at stageⅠ+Ⅱ;the positive expression rates of individualhMAM and combined with C-erbB2 were statistically significant(χ²=5.157, P<0.05; χ²=4.912, P<0.05). Conclusion: hMAM has a low positive rate in the diagnosis of micrometastases in the breast cancer patients,while hMAM combined with MMP-9 and C-erbB2 detectioncould improve the positive rates.which presents some clinical application value for the early diagnosis of breast cancer micrometastases.

Key words: breast neoplasms, micrometastases, human mammaglobin, matrix metallopeptidase 9, human epidermal growth factor receptor 2