Frequent S100A4 Expression Affects Invasive Tendency Of Colorectal Cancers

Backgrounds and Objectives: Colorectal carcinoma (CRC) is one of the commonest malignancies, although in China the morbidity is not as high as the rest region around the world. Recently along with the change of economic level, food propotion and life style in China, the morbidity and mortality increase rapidly. It has been demonstrated that the development of colorectal carcinoma is a multi-step, multi-factor process including genetical, environmental, and diet habit and so on. Because of lack of early detection, the early diagnosis and prognisis are very poor. Therefore, exploration of genetic alterations closely linked with colorectal carcinoma formation and dissemination would be of great values in prevention, early detection and prognostic evaluation of this malignancy.S100A4 is a metastasis-relating gene and closely related to biological behavior of malignant neoplasia through 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 lung, gastric, pancreas, bladder, thyroid cancer, and osteosarcoma malignant and induced to poor prognosis. Although the tumor-promoting effects of S100A4 have been documented in a variety of cancers, less report has been so far available concerning the S100A4 expression in colorectal carcinoma.Based on the above unclear issues, the current research aimed to profile expression of S100A4 during stepwise colorectal carcinoma and to analyze the relationship to the series of pathological factors.Materials and Methods:CRC and relative normal colorectal tissues were all selected from the Xinhua affliated hospital of Dalian University from 2008-2011. All the samples were conclusively diagnosed without chemoradiotherapy. By the methods of paraffin embedded tissue array immunohistochemistry, the expression pattern of S100A4 in different colorectal tissues were detacted, the correlation between S100A4 expression and invasiveness and metastasis was analyzed. The data were statistically analyzed by Kruskal-Wallis, Mamm Whitney and Spearmen with SPSS 11.5 software. Results:1. Expression of S100A4 in different colorectal tissues.The detection rate of S100A4 protein in relative noncancerous tissues and cancer samples were 9.5% and 64.5%, statistical analyses with Kruskal-Wallis test and Mann-Whitney test revealed the increasing tendency of S100A4 during the stepwise carcinogenesis (p=0.000). There were no significant differences of S100A4 expression between the tumor in colon and tomor in rectum (81.3%, 58.7%, p=0.107).2. The relationship of S100A4 expression and the pathological factors.2.1 60.6% of male and 69.0% of female showed positive S100A4 expression in colorectal cancer, which indicated no significant gender difference in expression of this protein (p=0.496). No statistical differences could be observed in different age group, gross type, and tumor size (p=0.268, p=0.568, p=0.621). There were significant differences in S100A4 expression among the high, middle and low differentiation level (p=0.028).2.2 Among 62 cases of colorectal carcinoma, 25 and 37 cases were LN negative and positive group respectively. The S100A4 protein labeled rate were 52.0% and 73.0%. Upregulation of S100A4 expression was closely related to lymphatic metastasis, the S100A4 expression in LN positive group was significantly higher than that in LN negative group (p=0.027). Higher expression rate of S100A4 were observed both throughout-layer invasion (72.4%) group rather than in muscular-layer invasion (57.6%) group, but no statistical significance (p=0.227).Conclusion: 1. The expression of S100A4 protein is an important molecular event in colorectal cancer. The upregulated S100A4 expression was shown from non-cancerous to cancer epithelial.2. The frequencies of S100A4 expression are unrelated to factors of gender, age, gross type and tumor size except the differentiation level. The lower differentiation shows the higher protein expression level. S100A4 expression in LN positive group was statistically significantly higher than that in LN negative group. The expression rate of S100A4 in throughout-layer invasion group is higher than in muscular-layer invasion group which indicate that S100A4 contributes to invasion and progression of colorectal cancer, and is of important value in molecular diagnosis and prognosis prediction.