6273

S100A2

S100 calcium binding protein A2;S100A2;S100 calcium binding protein A2

S100 calcium-binding protein A2|protein S100-A2

1q21

protein-coding

BACKGROUND AND AIM: Cholangiocarcinoma arising in the large bile ducts undergoes a multistep carcinogenesis process in chronic biliary diseases, and biliary intraepithelial neoplasia is known as a precursor lesion. This study examined the expression of S100 proteins in the multistep cholangiocarcinogenesis to clarify their clinicopathological significance. METHODS: Immunohistochemical analysis was performed for the expression of S100A2, S100A4, S100A6, and S100P. Bile concentrations of S100P were measured using enzyme-linked immunosorbent assay. RESULTS: The immunohistochemical expression of the S100 proteins was increased in biliary intraepithelial neoplasia as well as invasive adenocarcinoma of perihilar cholangiocarcinoma. Among the proteins, S100P expression was most drastically increased during the multistep carcinogenesis process. In cases with perihilar and extrahepatic cholangiocarcinoma, the immunohistochemical expression of S100A2 in cholangiocarcinoma cells significantly correlated with the histological grade, lymph node metastasis, clinical stage, and a poor survival rate of the patients. The bile levels of S100P were increased significantly in patients with cholangiocarcinoma compared with those in patients with lithiasis. Receiver operating characteristic curve analysis showed that S100P bile concentration was an indicator of cholangiocarcinoma with a sensitivity of 93% and a specificity of 70%. CONCLUSIONS: These results suggest that S100P may be useful for the detection of cholangiocarcinoma as tissue and bile biomarkers, and the immunohistochemical expression of S100A2 is a potential prognostic marker in cholangiocarcinoma patients.

PURPOSE: S100 proteins are implicated in metastasis development in several cancers. In this study, we analyzed the prognostic role of mRNA levels of all S100 proteins in early stage non-small cell lung cancer (NSCLC) patients as well as the pathogenetic of S100A2 in the development of metastasis in NSCLC. EXPERIMENTAL DESIGN: Microarray data from a large NSCLC patient cohort was analyzed for the prognostic role of S100 proteins for survival in surgically resected NSCLC. metastatic potential of the S100A2 gene was analyzed in vitro and in a lung cancer mouse model in vivo. Overexpression and RNAi approaches were used for analysis of the biological functions of S100A2. RESULTS: High mRNA expression levels of several S100 proteins and especially S100A2 were associated with poor survival in surgically resected NSCLC patients. Upon stable transfection into NSCLC cell lines, S100A2 did not alter proliferation. However, S100A2 enhanced transwell migration as well as transendothelial migration in vitro. NOD/SCID mice injected s.c. with NSCLC cells overexpressing S100A2 developed significantly more distant metastasis (64%) than mice with control vector transfected tumor cells (17%; P < 0.05). When mice with S100A2 expressing tumors were treated i.v. with shRNA against S100A2, these mice developed significantly fewer lung metastasis than mice treated with control shRNA (P = 0.021). CONCLUSIONS: These findings identify S100A2 as a strong metastasis inducer in vivo. S100A2 might be a potential biomarker as well as a novel therapeutic target in NSCLC metastasis.

The purpose of this study was to discover whether S100A2 expression is associated with late cervical metastasis in patients with stage I and II invasive squamous cell carcinoma of the oral cavity. We retrospectively investigated the clinicopathological parameters and S100A2 expression in surgical specimens taken from 52 patients with T1-2N0M0 invasive squamous cell carcinoma of the oral cavity (OSCC) who had not undergone elective neck dissection or irradiation to the neck. All of the clinicopathological factors and S100A2 expression were compared in terms of late cervical metastasis. In univariate analysis, late cervical metastasis correlated with poor overall survival. A higher rate of late cervical metastasis was observed in patients with S100A2-negative tumors than those with S100A2-positive tumors. Multivariate analysis on late cervical metastasis revealed that S100A2 expression was demonstrated to be the only independent factor for late cervical metastasis. Our results indicate that patients with stage I or II invasive OSCC without S100A2 expression should be considered a high-risk group for late cervical metastasis when a wait-and-see policy for the neck is being considered.

BACKGROUND & AIMS: Current methods of preoperative staging and predicting outcome following pancreatectomy for pancreatic cancer (PC) are inadequate. We evaluated the utility of multiple biomarkers from distinct biologic pathways as potential predictive markers of response to pancreatectomy and patient survival. METHODS: We assessed the relationship of candidate biomarkers known, or suspected, to be aberrantly expressed in PC, with disease-specific survival and response to therapy in a cohort of 601 patients. RESULTS: Of the 17 candidate biomarkers examined, only elevated expression of S100A2 was an independent predictor of survival in both the training (n = 162) and validation sets (n = 439; hazard ratio [HR], 2.19; 95% confidence interval [CI]: 1.48-3.25; P < .0001) when assessed in a multivariate model with clinical variables. Patients with high S100A2 expressing tumors had no survival benefit with pancreatectomy compared with those with locally advanced disease, whereas those without high S100A2 expression had a survival advantage of 10.6 months (19.4 vs 8.8 months, respectively) and a HR of 3.23 (95% CI: 2.39-4.33; P < .0001). Of significance, patients with S100A2-negative tumors had a significant survival benefit from pancreatectomy even in the presence of involved surgical margins (median, 15.7 months; P = .0007) or lymph node metastases (median, 17.4 months; P = .0002). CONCLUSIONS: S100A2 expression is a good predictor of response to pancreatectomy for PC and suggests that high S100A2 expression may be a marker of a metastatic phenotype. Prospective measurement of S100A2 expression in diagnostic biopsy samples has potential clinical utility as a predictive marker of response to pancreatectomy and other therapies that target locoregional disease.