Immunohistochemical Expression and Localization of Cytokines/chemokines/growth Factors in Gastric Cancer

Our previous studies on gastric cancer tissue and patient plasma samples identified several cytokines/chemokines/growth factors to be differentially expressed, compared to normal samples. In this study our aim was to understand the localization patterns of the markers in gastric tissues. We investigated the expression of PDGFRB, CCL3, MMP3, CXCL8, CXCL10, CCL20, IGFBP3, CXCL9, SPP1, CCL18, TIMP1, CCL15, CXCL5 and CCL4 in gastric tissues using Immunohistochemistry (IHC) on Tissue Microarrays (TMA). The TMA comprised of 25 apparently normal (AN), 87 paired normal (PN) and 134 gastric cancer (T) tissues. The epithelial and stromal expression of markers and their correlation with patient characteristics and outcome were analyzed. Several of the markers [PDGFRB (p<0.001), CCL3 (p<0.001), MMP3 (p<0.001), CXCL8 (p<0.001), CXCL10 (p<0.001), CCL20 (p<0.001), CXCL9 (p<0.001), CCL18 (p<0.001), TIMP1 (p=0.025), CCL15 (p<0.001)] were elevated in the stromal compartment of gastric cancers compared to AN tissues, with some having intermediate levels of expression in PN tissues. Epithelial and stromal PDGFRB (p=0.030, p=0.018) expression was associated with diffuse type gastric cancer. Stromal IGFBP3 (p=0.039), CXCL8 (p=0.008), TIMP1 (p<0.001), CCL4 (p=0.003) and SPP1 (p=0.048) expression was associated with intestinal type gastric cancer. Kaplan-Meier analysis showed higher epithelial PDGFRB (p=0.005 and p=0.004), CXCL8 (p=0.009 and p=0.007) were associated with poor disease free and overall survival. In multivariate analysis, high epithelial PDGFRB (p=0.036 and p=0.02) and SPP1 (p=0.003 and p<0.001) were independent prognostic factors for DFS and OS in patients with gastric cancer. The expression of cytokine/chemokine/growth factor markers is higher in the gastric tumor stroma compared to the normal gastric stroma and PDGFRB and SPP1 may serve as potential prognostic factors in gastric cancer.