Expression Of HLA-G Molecule In Esophageal Squamous Cell Carcinoma And Its Clinical Significance

Esophageal cancer is one of the most aggressive human malignancies and also is one of the most frequent causes of cancer death of the word.The highest mortality rate causing by esophagel cancer is found in China.The 2 main histopathologic types of esophageal cancer are squamous cell carcinoma (ESCC) and adenocarcinoma. In China, most are squamous. Surgical resection remains the standard treatment of resectable disease. Despite improvements in operative technique,prognosis of this disease is still poor, with an overall 5-year survival rate of less than 30% after standard esophagectomy,which is largely because of late disease presentation. Various studies have attempted to find markers that, by acting as useful adjuncts to morphologic and clinical features, could be used to predict the behavior of esophageal tumors. However, to date, none has been proven to be sufficiently reliable to be of practical use in the clinical setting.Human leukocyte antigen (HLA)-G is a unique non-classical HLA class I molecule expressed in immune-privileged sites and plays an essential role in the development of maternal tolerance to genetically different fetal tissues. HLA-G is predominantly expressed by the trophoblast, although ectopic expression is observed in certain situations, such as tumor cells. HLA-G expression has now been identified in most of the tumors, including colon cancer, melanoma, renal cancer, lung cancer, breast cancer, glioblastoma, and cutaneous lymphoma。The aberrant expression of HLA-G by tumor cells has been suggested to be part of the strategies they use to escape from the host's immunosurveillance.Interleukin 10 (IL-10) is a potential immune suppressive component during tumor development, and is a regulatory molecule for angiogenesis in ESCC cancers。Furthermore , IL-10 has been shown to induce HLA-G expression, and interestingly, HLA-G seems to in turn stimulate IL-10 expression。The discovery of HLA-G in these cancers led to our hypothesis that HLA-G could also play an important role in esophageal cancer carcinogenesis and could serve as an early diagnostic indicator。The expression of HLA-G in tumor and nontumor tissues was examined by RT-PCR and immunohistochemical staining. Concentrations of soluble HLA-G (sHLA-G)and IL-10 in patients'sera were examined by ELISA. Correlations with clinicopathologic factorswere made。In 60 patients with ESCC, intracellular HLA-G was overexpressed in esophagectomy specimens. The expression of HLA-G correlated with both tumor differentiation and lymph node status. Increased sHLA-G serum levels were also found and correlated with higher serum levels of IL-10,suggesting up-modulation of HLA-G by IL-10.These results demonstrate that human esophageal squamous cancer express and secrete large amounts of HLA-G. It is conceivable that HLA-G expression in esophageal cancer might be one of the ways how the tumor down-regulates host immune response, in addition to IL-10 production.HLA-G may serve as an autocrine factor in carcinogenesis and thus play an important role in the pathogenesis of ESCC.