The relationship between the tumor microenvironment of hepatocellular carcinoma and apparent diffusion coefficient.

616 Background: 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. Methods: 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. Results: 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%). Conclusions: 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.