| BackgroundEsophageal cancer(EC)is a highly aggressive solid tumor, which is characterized by late diagnosis and early metastasis. As one of the eight most common malignancies, about 480000 people was inflicted and 407000 deaths caused by EC in 2008, which accounts for 5.4% and ranks the 6th of total cancer deaths in the world. Esophageal squamous cell carcinoma(ESCC) is the major histological subtype of EC and is a representative of squamous cell carcinoma. The perioperative prognosis of ESCC has been improved due to the development of surgical and multimodal treatment strategies. However, the overall survival rate of ESCC is still not satisfactory and lag behind other gastrointestinal malignancies. Up to now, clinical staging remains one of the main factors to assess recurrence and overall survival.Recent studies indicate that intergrin β1 is a key factor involved in metastasis of malignant process of diverse types of cancer, such as larynx, lung, mammary gland, ootheca, bladder and skin. There is a significant difference of aberrant integrin β1 expression in malignant tumor tissues. The potential of infiltration and migration of malignant cells could be promoted when integrin β1 is over-expressed, down-regulated, configuration-altered or deleted. After activation by ligand binding, integrin β1 could subsequently promote formation of focal adhesion and activate focal adhesion kinase, which benefit angiogenesis in tumor tissue and is well related with the invasive growth and formation of metastatic tumor in distant organs. Although the mechanisms of integrin β1 function in metastasis is still unclear, recent studies have shown that integrin β1 is a molecule involved in adhesion and signaling, and play crucial roles in local invasion and metastasis. Our previous studies showed that the expression of integrin β1 in ESCC was significantly up-regulated, but the correlation beween integrin β1 and clinicopathological information, the postoperative survival is limited.In this study, the expression of integrin β1 in ESCC of stage TNMⅠ-Ⅳ was analysed using Western-blot, immunostaining in 100 cancer samples on a tissue microarray. In addition, the correlation between integrin β1 expression and clinical pathological data and the 5-year survival period after surgery were determined.AimsThe present study undertaken was to characterize the expression of integrin β1 in ESCC and to determine the correlation between aberrant integrin β1 expression with clinicopathological data and the 5-year survival period after esophagectomy.MethodsSixty ESCC froen samples of TNM stageⅠ-Ⅳ and paired margined nontumor tissue samples were randomly selected followed by protein extraction. Western blot analysis were performed to evaluate integrin β1 expression in tissue samples.IHC was used to assess integrin β1 expression in 100 cases of ESCC with 5-year follow-up data and the corresponding adjacent nontumor tissue. After immunostaining scoring and statistical analyses by SPSS software, the correlation between integrin β1 expsion with clinicopathological data and the 5-year survival period after esophagectomy was determined.Results1 Western-blot results showed that the expression of integrin β1 in ESCC of stage TNMI-IV was significantly higher than the corresponding nontumor marginal tissue samples. In addition, the expression of integrin β1 increased with progression of TNM stage and there was a positive correlation between integrin β1 expression and TNM stage(P<0.05).2 Immunohistochemical results showed that the frequencies of up-regulated integrin β1 expression were 33.3, 34.8, 35.7% in ESCC of well-, moderate- and poor-differentiation, respectively, without statistical significant difference(P=0.993).3 The frequencies of high integrin β1 expression in ESCC with clinical stage of TNMⅠ+Ⅱ, TNM Ⅲ+Ⅳ were 23.9%, 48% respectively, and the integrinβ1 expression was positively correlated with clinical stages(TNMⅠ+Ⅱ vs TNM Ⅲ+Ⅳ, P <0.05)。4 The frequencies of integrin β1 expression were 24.4%, 44.4% in positive and negative lymph node metastasis respectively, with no statistical significance(P =0.057).5 ROC curve analysis was performed to determine the cut-off value of immunostaining score to distinguish the deaths within 5 year and survivors. At the cut-off value of immunostaining score of 6.5, the area under ROC is 0.667 with a sensitivity of 0.420 and a specificity of 0.950.6 Kaplan-Meier survival analysis was performed to determine the correlation of integrin β1 expression with 5-year overall survival, and the results showed that up-regulation of integrin β1 was positively correlated with the shortened five-year survival(P<0.01).7 Cox regression analysis showed that integrin β1 is an independent factor for ESCC survival prediction(P<0.01).Conclusions1 Integrin β1 is an independent factor for ESCC survival prediction.2 Integrin β1 may be a novel molecular target to ESCC therapy. |
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