Expressions of chromogranin A and cathepsin D in human primary hepatocellular carcinoma.

AIM:To determine the expression and clinical significance of chromogranin A and cathepsin D in hepatocellular carcinoma (HCC).METHODS:Double immunofluorescence stain-ing techniques combined with laser confocal scanning microscopy (LSCM) was used to investigate chromogranin A and cathepsin D expressions in 85 HCC patients.RESULTS:Cathepsin D was expressed in 3 normal liver tissues, while in HCC the staining showed regional variation and the fraction of strongly stained cells increased as the tumors became less differentiated and usually clinically more malignant.Cells which showed strong positivity for cathepsin D were present in 71/85(83.5%) cases. Strong expression of cathepsin D in cancer cells was related to histopathological features. They were more common in grade 3-4 (26/28, 92.9%) and grade 2 (46/53, 86.8%) tumors than in grade 1 tumors (1/4, 25.0%)(P <0.01). No significant correlation was found between age and cathepsin D expression. In patients with positive cathepsin D reaction, the mean age was 52.1± 2.8 years (range 32-68 years) and in the group with negative reaction, the mean age was 51.3± 4.5 years (range 28-71 years). No obvious relationship was observed between CgA expression in cancer cells and the histopathological features. The CgA positive rate was 75.0% (3/4) in grade 1, 71.7% (38/53) in grade 2,and 71.4% (20/28) in grade 3-4(P >0.05) tumors. The coexpression of CgA and cathepsin D was found by double labeled immunofluorescence staining techniques. The processing of cathepsin D was disturbed in HCC cells and accumulated in the cells.Cathepsin D had proteolytic activity and autocrine mitogenic effect, suggesting their functions in invasion. These findings demonstrated that the expression of cathepsin D in HCC had prognostic value.CONCLUSION:Chromogranin A and cathepsin D are expressed in a high proportion of HCC and the existence of cathepsin D in HCC might be related to processing of CgA. This is clearly a subject for further studies because of its potential clinical applications.