[The prognostic analysis of hepatocellular carcinoma based on the tumor neo-vessels, macrophages and α-SMA in tumor microenvironment].

Objective

To analyze the quantitative expression and prognostic significance of tumor neo-vessels, macrophages and fibroblasts in tumor microenvironment of hepatocellular carcinoma (HCC).

Methods

The clinic-pathological features and tissue samples for 101 HCC cases were collected. Immunohistochemistry was used to stain the tumor neo-vessels, macrophages and fibroblasts on tumor tissue. The distribution results and quantitative data of above key components were acquired by inverted microscopy equipped with CRi Nuance multispectral analysis system. The number of tumor neo-vessels and macrophages on HCC tissue were counted and the thickness of cancer stroma based on the expression of fibroblasts was measured. The clinic-pathological characteristics and overall survival were analyzed.

Results

The median disease free survival (DFS) of 101 HCC cases was 5 month. The quantitative analysis of tumor neo-vessels, macrophages and fibroblasts showed that the expression range was 51-429 with median 218, 110-555 with median 259, 35.61-555.35 with median 246.98, respectively. To take the median as cutoff, all the cases could be classified into high and low expression group. The survival analysis demonstrated that the high density group of macrophages (P=0.022) and fibroblasts (P<0.001) has shorter DFS than low density group, with statistical significance. The high tumor neo-vessels group has shorter DFS with median 5 month than low density group with median 7 month. However, there was no statistical significance between these two group (P=0.197). Combined with above the three stromal components, all the cases could be classified into low, middle and high group. The survival analysis demonstrated that the high density group of stromal components has shorter DFS than the other two groups with median 3 month (P=0.001). Multivariate analysis by Cox regression indicated that cirrhosis, metastasis status, macrophages and fibroblasts density were the independent prognostic factors.

Conclusion

The key elements in tumor microenvironment including tumor neo-vessels, macrophages and fibroblasts were heterogenic in HCC tissues and played significant roles in HCC invasion and metastasis.