BackgroundWhile recent research has shown that expression of ZEB-1 in a variety of tumors has a crucial impact on patient survival, there is little information regarding ZEB-1 expression in hepatocellular carcinoma (HCC). This study investigated the co-expression of ZEB-1 and E-cadherin in HCC by immunohistochemistry and evaluated its association with clinical factors, including patient prognosis.MethodsA total of 108 patients with primary HCC treated by curative hepatectomy were enrolled. ZEB-1 expression was immunohistochemically categorized as positive if at least 1% cancer cells exhibited nuclear staining. E-cadherin expression was divided into preserved and reduced expression groups and correlations between ZEB-1 and E-cadherin expression and clinical factors were then evaluated.ResultsWith respect to ZEB-1 expression, 23 patients were classified into the positive group and 85 into the negative group. Reduced E-cadherin expression was seen in 44 patients and preserved expression in the remaining 64 patients. ZEB-1 positivity was significantly associated with reduced expression of E-cadherin (p = 0.027). Moreover, significant associations were found between ZEB-1 expression and venous invasion and TNM stage. ZEB-1 positivity was associated with poorer prognosis (p = 0.025). Reduced E-cadherin expression was significantly associated with intrahepatic metastasis and poorer prognosis (p = 0.047). In particular, patients with both ZEB-1 positivity and reduced E-cadherin expression had a poorer prognosis (p = 0.005). Regardless of E-cadherin status, ZEB-1 was not a significant prognostic factor by multivariate analysis. There was no statistical difference in overall survival when E-cadherin expression was reduced in the ZEB-1 positive group (p = 0.24).ConclusionsPositive ZEB-1 expression and loss of E-cadherin expression are correlated with poor prognosis in HCC patients and malignancy of ZEB-1 positive tumors involves EMT.

Cluster of differentiation (CD)68 may be used as a pan-macrophage or M1 marker, whereas CD163 may be used as an M2 marker. Furthermore, folate receptor (FR)β exhibits an M2-like functional profile. In the present study, CD68 and CD163 were used to evaluate and classify tumor-associated macrophages (TAMs). The expression of CD68, CD163 and FRβ by TAMs in hepatocellular carcinoma (HCC) Tissues was investigated. Samples from 105 patients with HCC were evaluated using immunohistochemistry. The results revealed that CD68 and CD163 overexpression was associated with a worse prognosis. The number of CD68 positive cells observed was significantly higher in patients with stage IV cancer. Furthermore, an increase in CD68 positive cells was observed in patients with median tumor size ≥3.5 cm and in patients with poorly differentiated HCC. The number of CD163 positive cells was also significantly increased in patients with median tumor size ≥3.5 cm and in those with poorly differentiated HCC. A low CD163/68 ratio was correlated with a worse outcome. The ratio was significantly lower in patients with stage IV cancer, patients with des-gamma-carboxy prothrombin abnormalities, patients with blood vessel infiltration and patients with intrahepatic metastasis. The number of FRβ positive cells was not correlated with clinicopathological features. The results of the present study indicate that overexpression of CD68 and CD163 may be associated with a worse patient outcome. The evaluation of CD68 and CD163 positive cells in a cancer microenvironment is controversial. TAMs are not simply cells with single markers or restricted M1 or M2 phenotypes; they are more diverse and heterogeneous. Further studies are required to determine the cross-interaction between diverse TAMs and the tumor microenvironment.

Lymphangiogenesis in primary tumors and draining lymph nodes is essential for efficient spread of tumor cells through the lymphatic system. Thus, inhibition of lymphangiogenesis could limit lymphatic dissemination of tumor cells.

Pure laparoscopic segmentectomy for HCC with a conventional puncture technique by ICG injection under laparoscopic US is considered to be a useful procedure featuring both low invasiveness and curative success.

MELK expression in HCC is extremely intense compared to its expression reported in other types of cancer. MELK could be a promising effective tumor marker of HCC and further consideration is needed.