Expression of CD68+ Tumor associated macrophages in relation to β-catenin in carcinoma stomach

Abstract

ABSTRACT Background: With no unified system for tumor associated macrophages (TAMs) density assessment, limited information is available on their relationship with β-catenin expression. Aim: To evaluate the density of CD68+ TAMs in gastric adenocarcinoma samples by immunohistochemistry and correlate it with grade, stage, invasion, and beta-catenin. Designs and Settings: Formalin fixed paraffin embedded (FFPE) blocks from gastrectomy specimens of proven gastric adenocarcinoma were prospectively and retrospectively were studied over a period of two years. Materials and Methods: Immunohistochemistry with CD68 and β-catenin was performed. TAM density was qualitatively compared in “tumor” versus “stroma” and “tumor” versus “non-tumor” regions. Quantitative CD68+ TAM density was assessed using different methods and compared. Cases were classified as high and low TAM based on the median value and correlated with histologic type, location, grade, stage and β-catenin expression pattern. Statistical Analysis: Spearman’s rank correlation test was used to compare the different methods of TAM density evaluation. The categorical variables were studied using Pearson’s Chi-square or Fisher’s exact test. CD68+ TAM density and β-catenin expression were correlated by analysis of variance. A P value ≤ 0.05 was taken as statistically significant. Results: The CD68+ TAMs in the “tumor” versus “non-tumor” area (p = 0.34) and “tumor” versus “stroma distribution” (p = 0.81) did not show any statistical significance. All methods of TAM density were found to be comparable. High TAM group is significantly associated with lymphovascular invasion, tumor depth, lymph node metastasis, and abnormal β-catenin expression. Conclusion: TAMs density plays an important role in the tumor stage. Macrophages may possibly induce gastric cancer invasiveness by activating β-catenin pathway.