Ito Y, Takeda T, Sakon M, Tsujimoto M, Higashiyama S, Noda K, Miyoshi E, Monden M, Matsuura N
Department of Surgery, Osaka Seamen's Insurance Hospital, 1-8-30, Chikko, Minato-ku, Osaka, 552-0021, Japan.
Br J Cancer. 2001 May 18;84(10):1377-83. doi: 10.1054/bjoc.2000.1580.
In order to elucidate the clinical significance of the erbB family, epidermal growth factor receptor (EGF-R), c-erbB-2, c-erbB-3 and c-erbB-4 in hepatocellular carcinoma (HCC), we investigated the expression of these proteins by means of immunohistochemistry for HCC as well as adjacent noncancerous lesions. EGF-R was expressed in 68% of the HCC examined and showed correlation with the proliferating activity, stage, intrahepatic metastasis and carcinoma differentiation. c-erbB-2 was expressed in only 21% of the cases and showed no relationships with the clinicopathological parameters. c-erbB-3 protein was observed in 84% of the HCC and 38.1% of the noncancerous lesions. Its expression in HCC was equal to or greater than noncancerous lesions in 90.5% of the cases, and was related to the stage, portal invasion, cell proliferating activity, tumour size, intrahepatic metastasis and carcinoma differentiation. c-erbB-4 protein was expressed in 61.0% of HCC and in as much as 86.1% of the noncancerous lesions. Unlike the expression of c-erbB-3, that of c-erbB-4 in HCC was less than that of the adjacent noncancerous lesions in 51.2% of the cases. No statistical significance could be established between this protein expression in HCC and clinicopathological features. EGF-R and c-erbB-3 affected disease-free survival, but were not recognized as independent prognostic factors by multivariate analysis. The present study suggests that, of the four receptors, EGF-R and c-erbB-3 play important roles in the progression of HCC.
为阐明表皮生长因子受体(EGF-R)、c-erbB-2、c-erbB-3和c-erbB-4在肝细胞癌(HCC)中的临床意义,我们采用免疫组织化学方法研究了这些蛋白在HCC以及相邻非癌性病变中的表达。在68%的检测HCC中检测到EGF-R的表达,且其表达与增殖活性、分期、肝内转移及癌分化相关。仅21%的病例检测到c-erbB-2的表达,且其与临床病理参数无关。在84%的HCC和38.1%的非癌性病变中观察到c-erbB-3蛋白。在90.5%的病例中,其在HCC中的表达等于或高于非癌性病变,且与分期、门静脉侵犯、细胞增殖活性、肿瘤大小、肝内转移及癌分化相关。61.0%的HCC及高达86.1%的非癌性病变中检测到c-erbB-4蛋白的表达。与c-erbB-3的表达不同,51.2%的病例中HCC中c-erbB-4的表达低于相邻非癌性病变。HCC中该蛋白表达与临床病理特征之间未发现统计学意义。EGF-R和c-erbB-3影响无病生存期,但多因素分析未将其认定为独立的预后因素。本研究提示,在这四种受体中,EGF-R和c-erbB-3在HCC进展中起重要作用。