Figure 1.
Connective tissue growth factor (CCN2), epithelial membrane antigen (EMA), fibroblast activation protein (FAP), and keratin 19 (K19) expression in hepatocellular carcinomas (HCCs) of cohort 1.
A) Small nests of tumor cells are surrounded by fibrous stroma. B) Immunohistochemistry for CCN2 exhibits diffuse cytoplasmic expression in tumor epithelial cells of HCC. C–D) Immunohistochemistry for EMA reveals patchy or focal expression pattern in tumor epithelial cells of HCC. E–F) K19 is focally positive in the periphery of tumor nests. (G–H) FAP is expressed in the cytoplasm of cancer-associated fibroblasts of tumor stroma. (Scale bars represent 100 µm.)
Table 1.
Clinicopathological characteristics of HCCs according to CCN2, EMA, and FAP expression in cohort 1 (n = 314).
Figure 2.
Connective tissue growth factor (CCN2), epithelial membrane antigen (EMA), fibroblast activation protein (FAP), and keratin 19 (K19) expression in liver cirrhosis.
A) Liver cirrhosis showing regenerative hepatic nodules and fibrotic septa with chronic inflammatory cells. CCN2 (B), EMA (C), and FAP (D) expression is negative in both hepatocytes and benign stromal cells from cirrhosis specimens. (Scale bars represent 100 µm.)
Figure 3.
Connective tissue growth factor (CCN2), epithelial membrane antigen (EMA), and fibroblast activation protein (FAP) expression in scirrhous hepatocellular carcinomas (HCCs with abundant fibrous stroma) of cohort 2.
A–C) CCN2 (B) is diffusely expressed in the nests of tumor epithelial cells, and the tumor stromal cells between the nests of tumor epithelial cells exhibit strong FAP expression (C). D–F) EMA is mainly expressed in the periphery (E, arrows) of large tumor nests in contact with FAP-expressing cancer-associated fibroblasts (CAFs) of tumor fibrous stroma (F, arrowheads). G–I) HCCs with small nests or a trabecular pattern show diffuse expression for EMA in the tumor epithelial cells (H), which are closely admixed with FAP-expressing CAFs of tumor stroma. (Scale bars represent 100 µm.)
Table 2.
Clinicopathological characteristics of scirrhous HCCs according to CCN2, EMA, and FAP expression in cohort 2 (n = 42).
Figure 4.
Disease-free survival (DFS) analysis of hepatocellular carcinoma (HCC) patients according to the expressions of connective tissue growth factor (CCN2), epithelial membrane antigen (EMA), and fibroblast activation protein (FAP).
A–C) DFS analysis of HCC patients in cohort 1. HCC patients with positive expression of CCN2 (A) exhibit a significantly worse DFS curve compared to those without (P = 0.005). There is no significant difference in DFS rate according expression of EMA (B) or FAP (C). D–F) DFS analysis of scirrhous HCC patients (cohort 2). CCN2 (D) and EMA (E) expression significantly influences DFS rates among scirrhous HCC patients (P = 0.023 and P = 0.048, respectively), whereas there is no significant difference in DFS rate according to FAP expression (F).
Table 3.
Univariate and multivariate analysis of disease-free survival rate for HCC in cohort 1.