不同肝病变组织中CD34、CD31、Ki-67的表达及意义

目的比较正常肝组织、慢性肝炎、肝硬化、肝细胞肝癌组织及肝转移腺癌中CD34、CD31、Ki-67不同表达,寻找有助于鉴别不同性质病变的生物学标记物.方法正常肝及病变肝组织标本共104例;其中,正常肝组织10例;慢生C型肝炎组织73例;肝硬化组织7例;肝细胞肝癌7例;结肠癌肝转移5例;乳腺癌肝转移2例.73例慢性C型肝炎组织全部为肝穿活检标本,其余组织均为手术切除标本.所有病例标本分别行CD34、CD31、Ki-67免疫组织化学染色,半定量评分系统评价染色结果.统计学分析结果数据.结果在非肿瘤组织,抗CD34阳性染色主要存在于汇管区,亦可见于汇管区周围的肝实质内血窦.阳性染色内皮细胞呈点状、线状、半环状及环状,散在或簇状分布.肿瘤组织内抗CD34阳性染色特征与非肿瘤组织相似,阳性染色血管在肿瘤组织内散布分布.CD34指数在各病变组中的表达排列顺序依次为:肝细胞肝癌>乳腺癌肝转移>结肠癌肝转移>肝硬化>慢性C型肝炎>正常肝组织,从正常肝组织至慢性肝炎至肝细胞肝癌,CD34表达明显增强.组织中,抗CD31阳性染色分布、定位、形态特征与CD34相似.CD31在慢性肝炎、肝硬化、肝细胞肝癌、结肠癌肝转移及乳腺癌肝转移组织中阳性表达率分别为:6.8%(5/73)、100%(7/7)、100%(7/7)、100%(5/5)、100%(2/2);肝癌组织中CD31染色强度明显大于非癌组织中,组间比较具有显著差异(P<0.05).Ki-67阳性染色细胞呈棕黄色核着色,散在分布于肝实质内.阳性染色细胞无形态特殊性,亦无分布上的特殊性.Ki-67在各病变组间的阳性表达率分别为:64.4%(47/73)、28.6%(2/7)、100%(7/7)、100%(5/5)、100%(2/2),其中以在结肠癌肝转移组织中表达最明显;组间比较具有非常显著差异(P<0.05).在正常肝脏、慢性C型肝炎、肝硬化、肝细胞肝癌CD34、CD31、Ki-67三种生物学标记物在同一标本同时表达的阳性率分别为:0%(0/0)、4.1%(3/73)、28.6%(2/7)、100%(7/7),CD34、CD31、Ki-67其中任两种同时表达的阳性率分别为0%(0/10)、63.0%(46/73)、100%(7/7)、100%(7/7).结论 CD34是慢性肝病、肝癌临床病理评价的指标之一,CD34与CD31、Ki-67同时分析有助于建立可靠的诊断.

SIGNIFICANCE OF CD34, CD31 AND Ki-67 EXPRESSIONS IN DIFFERENT LIVER DISEASES

Objective To compare the expressions of CD34, CD31 and Ki-67 among normal liver, chronic hepatitis, cirrhosis, hepatocellular carcinoma (HCC) and liver metastatic adenocarcinoma, and to search for valuable markers to distinguish different diseases of the liver. Method 104 samples including 10 cases of normal liver tissues, 73 chronic hepatitis C, 7 cirrhosis, 7 HCC, and 5 metastatic adenocarcinoma of the colon and 2 of the breast were involved in this study. The specimens of chronic hepatitis C were obtained by liver biopsy and the others by hepatotomy. All specimens were immunohistochemically stained with CD34, CD31 and Ki-67 antibodies. Semiquantitative score system was used to analyze the results. Result In nontumor tissues, anti-CD34 staining was mainly confined to small vessels in the portal area and also seen in sinusoids in the liver parenchyma near potral areas, with dotty, linear, semicircular and circular staining patterns. In tumor tissues, the characteristics of positive staining were similar to those in nontumor tissues. The CD34 labeling index (LI) was in the following order: HCC > breast metastatic cancer > colon metastatic cancer > cirrhosis > chronic hepatitis C > normal liver. The CD31 positive expression rates were 6.8% (5/73) in chronic hepatitis C, 100%(7/7) in cirrhosis, 100%(7/7) in HCC, 100%(5/5) in metastatic cancer of colon and 100%(2/2) in metastatic acncer of breast. Positive CD31 immunostaining with pale yellow vessels was mainly seen in liver parenchyma or tumor tissues. CD31 LI was higher in HCC than that in other tissues and there was a significant difference in different tissues (P<0.05). Ki-67 antigen labeling was localized to the nucleus with a fine brown granularity. Ki-67-positive cells did not show any morphological change, and neither was there any zonal distribution of these positive cells. Ki-67 positive expression was the strongest in colon metastatic cancer. The three markers were detected in 0%(0/10) normal liver, 4.1%(3/73) chronic hepatitis C, 28.6%(2/7) cirrhosis, and 100%(7/7) HCC, respectively, while any two of the three markers were detected in 0%(0/10) normal liver, 63.0%(46/73) chronic hepatitis C, 100%(7/7) cirrhosis, and 100%(7/7) HCC, respectively. Conclusion CD34 is one of the biological markers in the clinicopathological assessment of chronic liver diseases and HCC. The analysis of three markers of CD34, CD31 and Ki-67 at the same time will be helpful to establishing a reliable diagnosis.