组织蛋白酶D和嗜铬颗粒素A在人原发性肝细胞癌的表达意义

Significance of cathepsin D and chromogranin A expression in human primary hepatocellular carcinomas

目的探讨组织蛋白酶Ｄ和嗜铬颗粒素Ａ在人原发性肝细胞癌（ＨＣＣ）的表达及其意义．方法免疫荧光双标记染色技术结合激光扫描共聚焦显微镜观察ＨＣＣ８５例．结果组织蛋白酶Ｄ在正常肝细胞有弱表达，但在ＨＣＣ组织，组织蛋白酶Ｄ的表达显著增强，而且癌细胞荧光染色强度存在区域性差别，通常临床恶性程度越高、肿瘤分化越差，荧光染色较强的癌细胞越多．ＨＣＣ的组织学分级越高，组织蛋白酶Ｄ的表达越多．８５例ＨＣＣ中有７１例癌细胞呈组织蛋白酶Ｄ强阳性，阳性率８３５％．在组织学分级为３～４级的２８例中，组织蛋白酶Ｄ阳性的占２６例（阳性率９２９％）；组织学分级为２级的５３例中，有４６例阳性（阳性率８６８％）；而组织学分级为１级的４例中，仅有１例阳性（阳性率２５０％）．组织蛋白酶Ｄ阳性细胞的分布，在组织学分级不同的ＨＣＣ中有明显差别（Ｐ＜００１）．我们还发现组织蛋白酶Ｄ的表达与患者年龄无明显关系．有组织蛋白酶Ｄ表达的患者平均年龄为５１２岁±２８岁（３２岁～６８岁），无组织蛋白酶Ｄ表达的患者平均年龄为５１２岁±４５岁（２８岁～７１岁）（Ｐ＞００５）．组织学分级为１级的ＨＣＣＣｇＡ阳性率为７５０％（３／４），２级的阳性率７１?

AIM To investigate the expression and clinical significance of cathepsin D and chromogranin A in human primary hepatocellular carcinoma (HCC). METHODS Double immunofluorescence staining techniques combined with laser confocal scanning microscopy were used to study cathepsin D and chromogranin A expression in 85 HCC patients. RESULTS Cathepsin D was expressed in normal hepatocytes, 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 l tumors (1/4, 25 0%) ( P <0 01). There was no significant correlation between the age and cathepsin D expression. In cases 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 2 years ±4 5 years (range 28 years-71 years). No obvious relationship was observed between expression of CgA 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 tumors, and 71 4%(20/28) in grade 3-4 ( P >0 05). The coexpression of CgA and cathepsin D was found by double labeled immunofluorescence staining techniques. The results suggested that the processing of cathepsin D was disturbed in HCC cells and accumulated in the cells. Cathepsin D had proteolytic activity and autocrine mitogenic effect, both of which suggest some function in invasion. These findings demonstrated the expression of cathepsin D in HCC has some 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 worthing further studies because of its potential in clinical applications.