乳腺癌组织中基质金属蛋白酶-2、基质金属蛋白酶-9 表达与人乳头状瘤病毒16/18 感染的关系及其临床病理意义

目的探讨乳腺癌组织中基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-9(MMP-9)表达与人乳头状瘤病毒(HPV)16/18感染的关系及其临床病理意义。方法回顾性选取2015年3月至2018年5月蚌埠医学院第二附属医院收治的90例乳腺癌病人乳腺癌组织为研究对象(乳腺癌组)，同时选取同期该院85例良性乳腺疾病切除病变周围正常乳腺组织作为对照(对照组)。实时荧光定量逆转录聚合酶链反应(qRT-PCR)检测组织中MMP-2、MMP-9 mRNA表达水平；免疫组织化学法检测组织中MMP-2、MMP-9蛋白表达；采用原位杂交法检测HPV16/18感染情况。回顾性分析乳腺癌病人临床病理资料，比较MMP-2、MMP-9表达、HPV 感染与病人临床病理特征关系。结果乳腺癌组病人MMP-2、MMP-9 mRNA 表达水平(1.58±0.13、2.14±0.11)及其蛋白阳性表达率(77.78%、80.00%)均显著高于对照组(1.00±0.05、1.02±0.07、27.06%、17.65%)(P<0.05)；乳腺癌组HPV16/18-DNA阳性率［71.11%(64/90)］显著高于对照组［12.94%(11/85)］(P<0.05)；MMP-2、MMP-9表达及HPV16/18阳性表达均与淋巴结转移、临床分期、绝经状态、雌激素受体(ER)阳性相关(P<0.05)；MMP-2、MMP-9表达与HPV感染呈正相关(P<0.05)。结论乳腺癌病人乳腺癌组织中MMP-2、MMP-9表达水平明显升高，与HPV16/18感染呈正相关，均与病人临床病理特征密切相关。HPV感染可能引起基质金属蛋白酶表达增高，从而促进乳腺癌的发生发展。

Relationship between HPV16 / 18 infection and expression of MMP-2 and MMP-9 in breast cancer

Objective To investigate the relationship between the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in breast cancer and human papillomavirus (HPV) 16 / 18 infection and its clinicopathological significance.Methods The breast cancer tissue of 90 cases with breast cancer patients in The Second Affiliated Hospital of Bengbu Medical College from March 2015 to may 2018 were retrospectively selected as the study object (breast cancer group), and 85 cases of normal breast tissue around benign breast disease resection lesions in the hospital during the same period were selected as the control group(control group). Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the mRNA expressions of MMP-2 and MMP-9 in breast cancer tissues, immunohistochemistry was used to detect the protein expressions of MMP-2 and MMP-9 in breast cancer, and the infection of HPV16/18 was detected by in situ hybridization. The clinicopathological data of breast cancer patients were retrospectively analyzed, and the relationships between MMP-2 and MMP-9 expressions, HPV16/18 infection and clinicopathological characteristics were compared.Results The mRNA expression levels (1.58±0.13, 2.14±0.11) and protein positive expression rates (77.78%, 80.00%) of MMP-2 and MMP-9 in breast cancer group were significantly higher than those in control group (1.00±0.05, 1.02±0.07), (27.06%, 17.65%)] (P < 0.05). The positive rate 71.11% (64/90)] of HPV16/18-DNA in breast cancer group was significantly higher than that in control group 12.94% (11/85)] (P < 0.05). The expressions of MMP-2, MMP-9 and positive expression of HPV16/18 were significantly correlated with lymph node metastasis, clinical stage, menopausal status and estrogen receptor (ER) positive(P < 0.05). The expressions of MMP-2 and MMP-9 were positively correlated with HPV16/18 infection (P < 0.05).Conclusions The expression levels of MMP-2 and MMP-9 in breast cancer tissues are significantly increased, which were positively correlated with HPV16/18 infection, and were closely related to the clinicopathological characteristics of patients. HPV infection may increase the expression of matrix metalloproteinases, thus promoting the occurrence and development of breast cancer.