Wang H X, Qin C, Han F Y, Wang X H, Li N
Department of Clinical Immunology, Xinxiang Medical University, Xinxiang, China.
Department of Pathology, Xinxiang Medical University, Xinxiang, China.
Genet Mol Res. 2014 Jan 22;13(2):2817-26. doi: 10.4238/2014.January.22.6.
Malignant cells show increased invasion potency in vitro and in vivo. This process is considered to be mediated by matrix-metalloproteases (MMPs). Hypoxia-inducible factor-2α (HIF-2α) may upregulate MMP-2 expression; however, little is known about the correlation between HIF-2α and MMP-2 expressions in breast cancer. The current study investigated this correlation immunohistochemically according to various clinical and pathological features in 102 paraffin-embedded archival tissue block specimens from patients with breast cancer. HIF-2α and MMP-2 expression was detected in 60.8% (62/102) and 65.7% (67/102) of tumor samples, respectively. HIF-2α expression was significantly correlated with tumor size (P = 0.019), lymph node involvement (P = 0.035), and metastasis (P = 0.035). MMP-2 expression was significantly associated with lymph node involvement (P = 0.043) and metastasis (P = 0.003). Univariate analyses revealed that HIF-2α (P = 0.001) and MMP-2 (P = 0.000) expressions were significantly associated with a poorer survival rate, as well as tumor size, lymph node invasion, and distant metastasis. Multivariate analysis revealed that HIF-2α (P = 0.003) and the T-stage (P = 0.000) were independent prognostic factors of overall survival. Spearman correlation analysis revealed that HIF-2α and MMP-2 expressions were significantly correlated (r = 0.990; P = 0.041). These results suggest that high HIF- 2α expression is associated with poor overall survival in patients with breast cancer, indicating that HIF-2α could be a valuable marker of breast cancer progression.
恶性细胞在体外和体内均表现出增强的侵袭能力。这一过程被认为是由基质金属蛋白酶（MMPs）介导的。缺氧诱导因子-2α（HIF-2α）可能上调MMP-2的表达；然而，关于乳腺癌中HIF-2α与MMP-2表达之间的相关性知之甚少。本研究采用免疫组织化学方法，根据102例乳腺癌患者石蜡包埋存档组织块标本的各种临床和病理特征，对这种相关性进行了调查。肿瘤样本中HIF-2α和MMP-2的表达分别在60.8%（62/102）和65.7%（67/102）中被检测到。HIF-2α表达与肿瘤大小（P = 0.019）、淋巴结受累（P = 0.035）和转移（P = 0.035）显著相关。MMP-2表达与淋巴结受累（P = 0.043）和转移（P = 0.003）显著相关。单因素分析显示，HIF-2α（P = 0.001）和MMP-2（P = 0.000）表达与较差的生存率以及肿瘤大小、淋巴结侵犯和远处转移显著相关。多因素分析显示，HIF-2α（P = 0.003）和T分期（P = 0.000）是总生存的独立预后因素。Spearman相关性分析显示，HIF-2α和MMP-2表达显著相关（r = 0.990；P = 0.041）。这些结果表明，高HIF-2α表达与乳腺癌患者较差的总生存相关，提示HIF-2α可能是乳腺癌进展的一个有价值的标志物。
