Increased S100A4 expression combined with decreased E-cadherin expression predicts a poor outcome of patients with pancreatic cancer

Abstract

Abstract. The calcium-binding protein, S100A4, with an inverse association of E-cadherin, is known to correlate with prognosis in various cancers. In this study, we investigated the expression of the S100A4 and E-cadherin status in relation to the clinicopathological parameters of pancreatic cancer. The expression status of these two proteins was examined in 72 specimens of primary pancreatic carcinoma with immunohistochemistry. Fifty-six of 72 (78%) surgical specimens of primary pancreatic cancer were positive for S100A4 according to immunohistochemistry. Thirty-one (43%) specimens of pancreatic cancer showed positive expression of E-cadherin. The inverse association of S100A4 and E-cadherin expression was significant in the cancers (p<0.0001). The S100A4 expression correlated significantly with the pathological T stage and poorer prognosis (p=0.024). The 41 E-cadherin-negative cases showed poorer prognoses and a higher incidence of liver metastasis (p=0.0344, p=0.027). The 10 cases with S100A4-negative/Ecadherin-positive cancers showed a significantly better prognosis than the others (p<0.05). The histological grade (p=0.004), nodal status (p<0.0001) and S100A4-positive status (p=0.048) were highly significant independent prognostic predictors (p<0.05). These results suggest that S100A4 overexpression combined with reduced E-cadherin expression play important roles in tumor progression and metastasis in pancreatic cancer. The combined examination of these two molecules is useful in evaluating the outcome of pancreatic cancer patient.

Expression of CD24, P-cadherin and S100A4 in tumors of the ampulla of Vater

“…35 Consequently, several carcinomas were shown to express S100A4, including pancreatic carcinomas, bladder cancer and breast carcinoma. [36][37][38] Zhao and colleagues found S100A4 expression in a small series of extrahepatic cholangiocarcinomas (8/10 cases) and biliary high-grade dysplasia (5/6 cases) but not in any of the investigated normal mucosa samples (0/10 cases). 28 In our Immunophenotyping of ampullary tumors D Baumhoer et al series, strong immunoreactivity against S100A4 was also virtually absent in normal mucosa samples (1/122, 1%).…”

S100A4 Contributes to the Suppression of BNIP3 Expression, Chemoresistance, and Inhibition of Apoptosis in Pancreatic Cancer

“…We found that both S100A2 and S100A4 were capable of repressing BNIP3 promoter-driven luciferase activity f2-fold compared with the empty vector control. As the prevalence and magnitude of S100A4 overexpression in pancreatic cancer is significantly greater than that of S100A2, and S100A4 expression has been clinically correlated with a poor outcome for pancreatic cancer patients, we focused on this protein in subsequent studies (18)(19)(20).…”

Systematic review of immunohistochemical biomarkers to identify prognostic subgroups of patients with pancreatic cancer

“…A correlation between S100A4 expression levels and metastasis has been suggested in several human cancers, including breast, oesophageal, lung, pancreatic, colorectal, prostate and gastric tumours 170 -176 . Two studies found it to be an independent marker of adverse outcome in PDAC 50,73 . Recent in vitro data indicate that knockdown of S100A4 suppresses cell proliferation and the invasiveness of PDAC cells 177 .…”