Ren Yi, Law Simon, Huang Xin, Lee Ping Yin, Bacher Michael, Srivastava Gopesh, Wong John
Department of Surgery, University of Hong Kong Medical Centre, Queen Mary Hospital, Hong Kong.
Ann Surg. 2005 Jul;242(1):55-63. doi: 10.1097/01.sla.0000168555.97710.bb.
The objectives of this study were: 1) to examine the expression of macrophage migration inhibitory factor (MIF) in esophageal squamous cell carcinoma (ESCC); 2) to see if a relationship exists between MIF expression, clinicopathologic features, and long-term prognosis; and 3) to ascertain the possible biologic function of MIF in angiogenesis.
MIF has been linked to fundamental processes such as those controlling cell proliferation, cell survival, angiogenesis, and tumor progression. Its role in ESCC, and the correlation of MIF expression and tumor pathologic features in patients, has not been elucidated.
The expression of MIF in tumor and nontumor tissues was examined by immunohistochemical staining. Concentrations of MIF, vascular endothelial growth factor (VEGF), and interleukin-8 (IL-8) in patients' sera and in the supernatant of tumor cells culture were examined by ELISA. Correlations with clinicopathologic factors were made.
In 72 patients with ESCC, intracellular MIF was overexpressed in esophagectomy specimens. The expression of MIF correlated with both tumor differentiation and lymph node status. The median survival in the low-MIF expression group (<50% positively stained cancer cells on immunohistochemistry) and high expression group (>/=50% positively stained cancer cells) was 28.3 months and 15.8 months, respectively (P = 0.03). The 3-year survival rates for the 2 groups were 37.7% and 12.1%, respectively. MIF expression was related to microvessel density; increased MIF serum levels also correlated with higher serum levels of VEGF. In addition, in vitro MIF stimulation of esophageal cancer cell lines induced a dose-dependent increase in VEGF and IL-8 secretion.
These results demonstrate, for the first time, that human esophageal carcinomas express and secrete large amounts of MIF. Through its effects on VEGF and IL-8, MIF may serve as an autocrine factor in angiogenesis and thus play an important role in the pathogenesis of ESCC.
本研究的目的为：1）检测巨噬细胞移动抑制因子（MIF）在食管鳞状细胞癌（ESCC）中的表达；2）观察MIF表达与临床病理特征及长期预后之间是否存在关联；3）确定MIF在血管生成中的可能生物学功能。
MIF与诸如控制细胞增殖、细胞存活、血管生成及肿瘤进展等基本过程相关。其在ESCC中的作用以及患者中MIF表达与肿瘤病理特征的相关性尚未阐明。
采用免疫组织化学染色检测肿瘤组织和非肿瘤组织中MIF的表达。通过酶联免疫吸附测定（ELISA）检测患者血清及肿瘤细胞培养上清液中MIF、血管内皮生长因子（VEGF）和白细胞介素-8（IL-8）的浓度。分析其与临床病理因素的相关性。
在72例ESCC患者中，食管切除标本中细胞内MIF过度表达。MIF的表达与肿瘤分化及淋巴结状态均相关。低MIF表达组（免疫组织化学染色阳性癌细胞<50%）和高表达组（免疫组织化学染色阳性癌细胞≥50%）的中位生存期分别为28.3个月和15.8个月（P = 0.03）。两组的3年生存率分别为37.7%和12.1%。MIF表达与微血管密度相关；MIF血清水平升高也与较高的VEGF血清水平相关。此外，体外对食管癌细胞系进行MIF刺激可导致VEGF和IL-8分泌呈剂量依赖性增加。
这些结果首次证明，人食管癌表达并分泌大量MIF。通过其对VEGF和IL-8的作用，MIF可能作为血管生成中的自分泌因子，从而在ESCC的发病机制中发挥重要作用。
