应用双色FISH技术检测肝癌中HER—2的定量扩增及其临床意义

为探讨原发性肝细胞癌(HCC)中原癌基因HER-2的扩增激活情况及其与临床病理特征和预后的关系,应用双色荧光原位杂交(dualFISH)技术检测42例原发性肝癌间期细胞核中HER-2的扩增和17号染色体的数目及其比值,并用统计学分析HER-2的扩增与临床病理特征及预后的相关性.结果在42例肝癌中有9例HER-2扩增(amplification),占21.4%,其中高拷贝扩增(HC)有4例(9.5%),低拷贝扩增(LC)有5例(11.9%),HER-2的扩增与性别、年龄、AFP水平、HBV感染、术后复发及临床分期无关(P＞0.05),而与术后2年生存期相关(P=0.046)且HER-2扩增病人的肿瘤有比无扩增病人的肿瘤增大的倾向(P=0.085);同时,在42例肝癌中有3l例为HER-2拷贝数增加(gain),占73.8%,其中9例(21.4%)为扩增所致,22例(52.4%)为17号染色体多倍体或异倍体(polysomy17/aneusomy17)所致,HER-2拷贝数增加与性别、临床分期、肿瘤大小、术后复发及术后2年生存期无关(P＞0.05),但与年龄、AFP水平和HBV感染有关(P＜0.05).以上结果提示原发性肝癌中存在较低频的HER-2癌基因扩增激活及较高频的17号染色体异倍体/多倍体;HER-2癌基因的扩增激活可能与部分肝癌的发生发展有关,是肝癌术后生存期短的有价值独立预后因子.

Quantitative Detection of HER-2Oncogene Amplification in Primary Hepatocellular Carcinoma Using Dual FISH Technique and Its Clinical Significance

To investigate the frequency of HER-2 oncogene amplification in primaty hepatocellular carcinoma (HCCs) and its relationships with clinicopathological parameters and prognosis, 42 surgical samples from patients with primary HCCs were detected for their HER-2 oncogene amplification by dual FISH technique, and then the correlations between HER-2 amplification and clinicopathological characteristics and prognosis were analyzed statistically. HER-2 oncogene amplification was detected in 9 of 42 (21.4%) primary HCCs, including 4 (9.5%) cases with high copy (HC) and 5 (11.9%) ones with low copy (LC). HER-2 amplification was associated significantly with postoperative survival time of HCC patients examined (P = 0.046) and the presence of HER-2 gene amplification showed a trend toward a correlation with tumor size (P = 0.085), but wasn' t relative to sex, age, AFP level, HBV infection, postoperative relapse and clinical staging of HCC patients tested (P> 0.05). On the other hand, gain of the HER-2 oncogene copy was examined in 31 of 42(73.8%) primary HCCs, consisting of 9 (21. 4%) cases with HER-2 amplification and 22(52.4%) ones with aneusomy 17/polysomy 17. There weren't significant relationships between gain of HER-2 oncogene copy and, HCC patient's sex, tumor size, clinical staging, postoperative relapse and survival time (P> 0.05), but gain of HER- 2 oncogene copy correlated significantly to patients'age, AFP level and HBV infection (P < 0.05). The study indicated that there were a lower frequency of HER-2 oncogene amplification and a higher frequency of aneusomy 17/polysomy 17 in primry HCCs and that HER-2 oncogene amplification activation might be involved in the development and progression of a subset of HCCs, and seemed to be a valuably independent prognosis factor predicting postoperative poorer survival for patients with HCC.