Consistency study of two methods in detection of human epidermal growth factor receptor-2 in breast cancer
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摘要:
目的 对比分析免疫组织化学法（immunohistochemistry，IHC）和荧光原位杂交法（fluorescence in situ hybridization，FISH）对乳腺癌人类表皮生长因子受体2（human epidermal growth factor receptor-2，HER-2）检测的一致性评价。 方法 选取2013―2018年入住安徽省某三级甲等医院并确诊患乳腺癌的患者组织，分别采用IHC及FISH两种方法检测HER-2，对比其结果的差异及联系。 结果 在选取的276例乳腺癌患者体内发现FISH法检测HER-2扩增与乳腺癌组织学分级相关。IHC法检测HER-2结果为3+的病例与同时做FISH检测结果为阳性扩增的符合率可以达到90%以上。当IHC为-/+和3+时，2种方法检测结果的一致性最好。而HER-2检测为2+的病人，与FISH检测方法相比，两者的符合率仅为67.9%。 结论 HER-2基因扩增与乳腺癌的恶性程度增高有关，IHC筛查HER-2检测结果为2+乳腺癌需加做FISH检测，对于乳腺癌患者的进一步诊疗具有指导意义。 -
关键词:
- 乳腺癌 /
- 人类表皮生长因子受体2 /
- 免疫组织化学法 /
- 荧光原位杂交法
Abstract:Objective To evaluate the consistency of immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) for the detection of human epidermal growth factor receptor-2 (HER-2) in breast cancer. Methods The patients who were diagnosed with breast cancer in a third-class A hospital in Anhui Province from 2013 to 2018 were selected. IHC and FISH were used to detect HER-2, and the differences and connections were compared. Results In the selected 276 breast cancer patients, FISH detection of HER-2 amplification was related to the histological grade of breast cancer. For patients with HER-2 of 3+ detected by IHC, the positive amplification rate of FISH could reach higher than 90%. When IHC was -/+ and 3+, the consistency of detection results between the two methods was the best.For patients with 2+ in HER-2 test, compared with FISH test, the coincidence rate of IHC was only 67.9%. Conclusions HER-2 gene amplification is associated with increased malignancy of breast cancer, HER-2 screening results of 2+ breast cancer by IHC requires additional FISH test, which is of guiding significance for the further diagnosis and treatment of patients. -
图 1 HER-2蛋白表达代表性染色和FISH检测HER-2基因扩增结果
Figure 1. The results of the representative staining of HER-2 protein expression and HER-2 gene amplification detected by FISH corn
表 1 IHC法检测HER-2着色判读标准
Table 1. Coloring interpretation criteria for HER-2 detected by IHC
IHC结果 IHC着色判读标准 IHC-阴性 无染色或≤10%的浸润性癌细胞呈现不完整的、微弱的膜染色 IHC+阴性 ＞10%的浸润性癌细胞呈现不完整的、微弱的膜染色 IHC2+阳性(不确定) ＞10%的浸润性癌细胞呈现弱-中等强度的、完整细胞膜染色或≤10%的浸润性癌细胞呈现强而完整的膜染色， IHC3+阳性 ＞10%的浸润性癌细胞呈现强、完整、均匀的膜染色 
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表 2 FISH法检测HER-2结果判定标准
Table 2. Criteria for HER2 detection by FISH method interpretation criteria
HER-2/CEP比值 平均HEP-2拷贝数 FISH结果 HER-2/CEP17比值≥2.0 平均HER-2拷贝数≥4.0信号/细胞 原位杂交阳性 平均HER-2拷贝数 < 4.0信号/细胞 原位杂交阴性 HER-2/CEP17比值< 2.0 平均HER-2拷贝数≥6.0信号/细胞 原位杂交阳性 平均HER-2拷贝数≥4.0且 < 6.0信号/细胞 结果要对比IHC结果再做最后判断 平均HER-2拷贝数 < 4.0信号/细胞 原位杂交阴性
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表 3 乳腺癌组织中HER-2基因扩增与临床病理因素的关系[n (%)]
Table 3. Relationship between HER-2 gene amplification and clinical pathological factors in breast cancer[n (%)]
病理特征 总例数 HER-2 FISH检测 χ2值 P值 阳性 阴性 年龄(岁) 2.487 0.115 < 50 132 42(31.82) 90(68.18) ≥50 144 59(40.97) 85(59.03) 肿瘤部位 -a 0.654 左乳 144 56(38.89) 88(61.11) 右乳 131 45(34.35) 86(65.65) 胸壁 1 0(0.00) 1(100.00) 组织学分级 -a 0.027 导管内癌 6 1(16.67) 5(83.33) 浸润性导管癌Ⅰ级 9 2(22.22) 7(77.78) 浸润性导管癌Ⅱ级 107 30(28.03) 77(71.97) 浸润性导管癌Ⅲ级 154 68(44.16) 86(55.84) 注：a表示采用Fisher's确切概率法。
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表 4 FISH法和IHC法检测HER-2结果比较
Table 4. Comparison of the results of FISH and IHC in detecting HER-2
FISH法 IHC法 χ2值 P值 -/+ 2+ 3+ - 14 159 2 38.547 < 0.001 + 1 78 22 合计 15 237 24
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