The relationship between the tumor microenvironment of hepatocellular carcinoma - including cancer-associated fibroblasts and tumor-associated macrophages - and apparent diffusion coefficient.

Abstract

The tumor microenvironment is critical for the acquisition of tumor malignancy in various cancer types. The objectives of this study were to investigate whether the levels of cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs) reflect the prognosis of patients with hepatocellular carcinoma (HCC) after hepatectomy (Hx) and to determine whether the apparent diffusion coefficient (ADC) from diffusion-weighted imaging (DWI) reflects CAF and TAM expression. The study cohort comprised 109 patients who underwent initial curative resection for HCC. Alpha smooth muscle actin (αSMA) was selected as a CAF marker and CD204 as a TAM marker. Protein expression was immunohistochemically evaluated in the intratumoral regions of resected specimens. Clinicopathological factors, including the long-term prognosis after Hx, were investigated between αSMA-negative and -positive tumors and between CD204-negative and -positive tumors. The correlation between CAF/TAM marker expression and the calculated minimum ADC using DWI was also evaluated. αSMA-positive expression was correlated with tumor number, invasive growth pattern, and advanced stage. CD204-positive expression was correlated with the presence of venous invasion. Both αSMA-positive expression and CD204-positive expression were significant prognostic factors in the univariate analysis of overall survival and disease-free survival. αSMA/CD204 double positivity was associated with an extremely poor prognosis after Hx and was a significant independent prognostic factor for overall survival (P=0.02, hazard ratio: 3.27). Patients with double positivity also showed a significantly higher ADC^low rate (83%). In conclusion, expression of both CAF and TAM markers reflected a poor prognosis after Hx. Furthermore, the preoperative ADC could be a clinical surrogate marker in the tumor microenvironment in patients with HCC.