CD138和乙酰化肝素酶在肝细胞癌中表达的组织芯片研究

Study of expression of CD138 and heparinase in hepatocellular carcinoma by tissue microarray

目的探讨人肝细胞癌中CD138和乙酰化肝素酶的表达水平及其与肝细胞癌发生、发展、转移和复发的关系。方法运用组织芯片技术,通过免疫组织化学EnVision法研究197例肝细胞癌、癌旁肝组织及其中66例转移病灶中CD138和乙酰化肝素酶的表达水平。48例获得4～72个月随访。结果(1)CD138的表达率在肝细胞癌和癌旁肝组织中分别为48.7%(96/197)和65.0%(128/197,P<0.05),在早期和中晚期肝细胞癌中分别为61.7%(29/47)和44.7%(67/150,P<0.05),在有和无转移的中晚期肝细胞癌组中分别为33.3%(22/66)和53.6%(45/84,P<0.05),在1年之内和1年之上复发组中分别为23.3%(7/30)和61.1%(11/18,P<0.05);(2)乙酰化肝素酶的阳性表达率在肝细胞癌和癌旁肝组织中分别为35.5%(70/197)和12.7%(25/197,P<0.05),在早期和中晚期肝细胞癌中分别为29.8%(14/47)和37.3%(56/150,P>0.05),在伴随和不伴转移的肝细胞癌组织中48.5%(32/66)和28.6%(24/84,P<0.05),在1年之内和1年之上复发组中分别为50.0%(15/30)和44.4%(8/18,P>0.05);(3)66例伴随转移的肝细胞癌组织中,CD138在乙酰化肝素酶阴性组中的高表达率高于阳性组(P<0.05)。结论(1)CD138在肝细胞癌组织中的低表达与其发生、发展、转移和复发密切相关,与分级、HBV感染及血清甲胎球蛋白值无关;(2)CD138蛋白低表达与乙酰化肝素酶高表达参与肝细胞癌的转移过程。

Objective To study the expression of CD138 and heparinase in hepatocellular carcinoma （HCC） and its relationship with tumor development, progression, metastasis and recurrence. Methods Tissue microarray and immunohistochemical study （ EnVision method） for CD138 and heparinase was performed on tissue microarray which consisted of 197 cases of HCC, including adjacent non-neoplastic liver tissues, and 66 cases of HCC metastases. Results The rates of CD138 expression in HCC and adjacent non-neoplastic liver tissues were 48. 7% （96/197） and 65.0% （128/197, P 〈 0.05 ） respectively. In early-stage and late-stage tumors, the expression rates were 61.7% （29/47） and 44. 7% （67/150, P 〈0.05 ） respectively. The rate in patients with metastasis was 33.3% （22/66） , as compared with 53. 6% （45/84, P 〈0. 05） in patients without metastasis. In patients with tumor recurrence occurring within or after 1 post-operative year, the expression rates were 23.3% （7/30） and 61.1% （ 11/18, P 〈 0. 05） respectively. On the other hand, the rates of expression of heparinase in HCC and adjacent nonneoplastic liver tissues were 35.5% （70/197） and 12. 7% （25/197, P 〈 0. 05 ） respectively. In earlystage and late-stage tumors, the expression rates were 29. 8% （ 14/47 ） and 37. 3% （ 56/150, P 〉 0. 05 ） respectively. The rate in patients with metastasis was 48.5% （32/66） , as compared with 28.6% （24/84, P 〈 0. 05 ） in patients without metastasis. In patients with tumor recun^nce occurring within or after 1 postoperative year, the expression rates were 50.0% （15/30） and 44. 4% （ 8/18, P 〉 0. 05 ） respectively. In the 66 cases of metastatic HCC studied, the expression rate of CD138 was lower in the heparinase-positive subgroup （P 〈 0. 05 ）. Conclusions Loss of CD138 expression is related to HCC development,progression, metastasis and recurrence. Overexpression of heparinase, when coupled with loss of CD138 expression, may take part in tumor metastasis of HCC.