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

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

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（ｄｕａｌ ＦＩＳＨ）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３１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（ｐｏｌｙｓｏｍｙ １７／ａｎｅｕｓｏｍｙ １７）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．

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.