Yusof Yasmin Anum Mohd, Yan Khong Li, Hussain Sharifah Noor Akmal Syed
Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300, Kuala Lumpur, Malaysia.
Anal Quant Cytol Histol. 2003 Dec;25(6):332-8.
To determine whether tumor marker pi glutathione transferase (GST-pi) is expressed in hepatocellular carcinoma (HCC) and other chronic liver diseases and to compare its expression with that of alpha-fetoprotein (AFP).
Samples used were formalin-fixed, paraffin-embedded liver tissues: normal (n = 3), chronic hepatitis B (n = 15), cirrhosis (n = 15) and HCC (n = 30). The expression of AFP and GST-pi was detected by using immunohistochemistry with the peroxidase-antiperoxidase method. AFP immunoreactivity was based on the cytoplasm of the hepatocytes, while GST-pi immunoreactivity was based on the nuclei of hepatocytes.
In normal liver tissues, AFP was not expressed. However, there was strong staining of GST-pi in bile duct epithelium cells and weak staining in hepatocytes. Our results showed higher AFP immunoreactivity in cases of HCC (36.7%) as compared to cirrhosis (6.7%) and hepatitis B (0%), whereas GST-pi immunoreactivity was lower in cases of HCC (53.3%) as compared to cases of cirrhosis (100.0%) and hepatitis B (93.3%). Percent sensitivity of AFP determination for HCC was 36.7% as compared to 53.3% for GST-pi, thus making GST-pi a more sensitive marker for detection of HCC. This study showed a significant relationship between the intensity and percentage of cells stained in hepatitis B, cirrhosis and HCC for GST-pi immunoreactivity (P < .001, .001 and .05, respectively) but not for AFP (P > .05). Statistical analysis showed that there was no significant relationship between expression of AFP and GST-pi in cirrhosis and HCC cases. Hepatitis B virus infection in HCC cases showed a positive rate of 46.7%, with AFP staining positively in 42.9% of tissues and GST-pi staining positively in 57.1% of tissues.
AFP is a diagnostic but rather insensitive tissue marker for HCC. However, the absence of AFP in benign chronic liver disease makes this marker useful in differentiating between HCC and other chronic liver diseases, whereas GST-pi can be used as a diagnostic marker for HCC as well as in detecting other chronic liver diseases.
确定肿瘤标志物π谷胱甘肽转移酶(GST-π)在肝细胞癌(HCC)及其他慢性肝病中是否表达,并将其表达情况与甲胎蛋白(AFP)进行比较。
所用样本为经福尔马林固定、石蜡包埋的肝组织:正常肝组织(n = 3)、慢性乙型肝炎(n = 15)、肝硬化(n = 15)及肝细胞癌(n = 30)。采用过氧化物酶-抗过氧化物酶法免疫组化检测AFP和GST-π的表达。AFP免疫反应基于肝细胞的细胞质,而GST-π免疫反应基于肝细胞的细胞核。
在正常肝组织中,AFP未表达。然而,GST-π在胆管上皮细胞中有强染色,在肝细胞中有弱染色。我们的结果显示,与肝硬化(6.7%)和乙型肝炎(0%)相比,肝细胞癌病例中AFP免疫反应性更高(36.7%);而与肝硬化(100.0%)和乙型肝炎(93.3%)相比,肝细胞癌病例中GST-π免疫反应性更低(53.3%)。AFP对肝细胞癌的检测敏感性为36.7%,而GST-π为53.3%,因此GST-π是检测肝细胞癌更敏感的标志物。本研究显示,乙型肝炎、肝硬化和肝细胞癌中GST-π免疫反应性的染色强度和细胞百分比之间存在显著相关性(分别为P <.001、.001和.05),而AFP不存在这种相关性(P >.05)。统计分析表明,在肝硬化和肝细胞癌病例中,AFP和GST-π的表达之间无显著相关性。肝细胞癌病例中乙型肝炎病毒感染的阳性率为46.7%,AFP染色阳性的组织占42.9%,GST-π染色阳性的组织占57.1%。
AFP是肝细胞癌的一种诊断标志物,但敏感性较低。然而,良性慢性肝病中AFP阴性使得该标志物在鉴别肝细胞癌和其他慢性肝病方面很有用,而GST-π既可用作肝细胞癌的诊断标志物,也可用于检测其他慢性肝病。