| Backgrounds and Objectives:Esophageal cancer (EC) is one of the commonest six malignancies in the world and, especially in China with higher morbidity and mortality. There are 300 thousand newly EC patients in the world among which half of them happen in China. So the esophageal cancer is one of the main malignancies for prevention and cure in China. It has been demonstrated that the development of EC is a multi-step process including normal mucosa, precancerous lesions (hyperplasia of basal cell, anaplastia and cancer in situ), EC (early carcinoma and infiltrating carcinoma). The exact mechanism leading to EC hasn't been fully understood, and the lack of accurate and effective method for early diagnosis plays the key role to induce the high mortality of EC. Therefore, exploration of genetic alterations closely linked with EC formation and dissemination would be of great values in prevention, early detection and prognostic evaluation of this malignancy.Multiple genes have been known to participate in the complicated process of esophageal carcinogenesis and cancer infiltation. By serial analysis of gene expression (SAGE), S100A4 is found to be a metastasis-relating gene and closely related to biological behavior of malignant neoplasia.S100A4 protein exerts multiple biological effects on proliferation and apoptosis, cell motility and adhesion, extracellular matrix remodeling, and angiogenesis of cancer cells. Frequent expression of S100A4 was observed in breast, colorectum, pancreas, bladder, thyroid cancer, osteosarcoma and malignant melanoma and related to poor prognosis. Transfection of S100A4 could enhance metastatic potential of bladder and mammary carcinoma cells, while blockage of its expression reduced cancer metastatic capacity. Although the tumor-promoting effects of S100A4 have been documented in a variety of cancers, no report has been so far available concerning the S100A4 expression in EC. Based on the above unclear issues, the current study aimed to profile expression of S100A4 during stepwise esophageal carcinogenesis and to analyze the relationship to the series of pathological factors. Materials and Methods:EC, precancerous lesions and relative normal esophageal tissues were all selected from the Anshan City Tumour Hospital from 1999-2008. All the exairesis samples were conclusive diagnosed without chemoradiotherapy. By the methods of paraffin embedded tissue array immunohistochemistry, the expression pattern of S100A4 in different esophageal tissues were detacted, the correlation between S100A4 expression and EC invasiveness and metastasis was analyzed. The data were statistically analyzed by Kruskal-Wallis, Mamm Whitney and Spearmen with SPSS 11.0 software.Results:1. The analysis of gender, age and histological type in esophageal carcinoma sample group.Among 83 cases of esophageal carcinoma, 68(81.2%) were esophageal squamous cell carcinoma (ESCC) and 15(18.8%) were adencarcinoma, 72(84.3%) were male patients and 13(15.7%) were female which indicated the higher morbidity of EC in male group. Among 68 ESCC cases, 63 were male and only 5 were female, but 7 of male and 8 of female were adencarcinoma, which manifested the gender difference (p=0.000) of morbidity in ESCC and adencarcinoma, but no difference in age factor.2. Expression characteristics of S100A4 in different EC tissues.It was found that the detection rate of S100A4 in noncancerous tissues, premalignant tissues and cancer samples were 22.2%, 26.3% and 59%, statistical analyses with Kruskal-Wallis test and Mann-Whitney test revealed the increasing expression tendency of S100A4 during the stepwise esophageal carcinogenesis (p=0.001). There were significant differences of S100A4 expression both between the EC group and noncancerous mucosa or premalignant lesions (p=0.032, p=0.001), and between the ESCC and adencarcinoma group (p=0.015), but not between noncancerous and premalignant epitheial. Some of the EC displayed focal hetergenerous distribution of S100A4 protein.3. The relationship of S100A4 expression and the pathological factors.54.3% of male and 84.6% of female showed positive S100A4 expression in EC, which indicated a significant gender difference in expression of this protein (p=0.042). No statistical differences could be observed in different age group, differentiation level tumor size (p=0.864, p=0.548, p=0.167).Among 83 cases of esophageal carcinoma, 39 and 44 cases were LN negative and positive group respectively. The S100A4 protein labeled rate were 46.2% and 70.5%. Upregulation of S100A4 expression was closely related to EC lymphatic metastasis, the S100A4 expression in LN positive group was significantly higher than that in LN negative group (p=0.026). Higher expression rate of S100A4 were observed both in T3,4 (65.5%)group rather than in T1,2 (44%) group, and the III-IV stage (70%) rather than I-II stage (48.8%), but no statistical significance in the latter two factors (p=0.069, p=0.051).Conclusion:1. ESCC is the main pathological type in EC with higher morbidity in male. The adencarcinoma were in low percentage with more female morbidity than the male.2. The expression of S100A4 gene is an important molecular event throughout the whole esophageal tumorigenesis, development and dissemination. The expression frequency increases from noncancerous, precancerous and cancer epithelial, especially in adencarcinoma.3. The frequency of S100A4 expression of female are higher than that of male, but unrelated to factors of age, differentiation and tumor size. S100A4 expression in LN positive group was statistically significantly higher than that in LN negative group. Higher expression rate of S100A4 in T3,4 group rather than in T1,2 (44%) group, in III-IV stage rather than in I-II stage which indicate that S100A4 contributes to invasion and progression of EC. and is of important value in molecular diagnosis and prognosis prediction. |
PDF Full Text Request