双色银染原位杂交与荧光原位杂交在乳腺癌HER2基因状态评估中的比较

Assessment of HER2 gene amplification in breast cancer： a comparison of dual-color in-situ hybridization and fluorescence in-situ hybridization

目的比较双色银染原位杂交（DISH）与荧光原位杂交（FISH）检测乳腺癌HER2基因状态的符合率，评价DISH法临床应用的可行性。方法对110例免疫组织化学HER2检测结果为2＋、并经FISH检测明确HER2基因状态的乳腺浸润性导管癌行DISH检测，分别用2007版和2013版美国临床肿瘤学会／美国病理医师学院（ASCO／CAP）HER2判断标准比较DISH和FISH检测结果的一致性。结果（1）采用2007版判断标准，DISH与FISH的总符合率为97．3％（107／110），其中51例FISH阳性病例DISH检测结果为50例阳性和1例不确定；10例FISH不确定病例中DISH8例为不确定，2例为阴性；49例FISH阴性者DISH均为阴性；符合率分别为98．0％、8／10和100．0％。（2）采用2013版判断标准，DISH与FISH的总符合率为90．0％（99／110），其中55例FISH阳性病例中DISH53例阳性、1例不确定、1例阴性；12例FISH不确定病例中DISH2例阳性、3例不确定、7例阴性；43例FISH阴性者DISH均为阴性；符合率分别为96．4％、3／12和100．O％。Pearson相关性分析显示FISH与DISH两种方法的检测结果显著相关（R=0．584，P〈0．01）。结论DISH检测HER2基因状态与FISH检测结果具有较高的符合率，可作为评估乳腺癌HER2基因状态的新选择。对于FISH检测不确定病例易产生不一致的临床意义尚待深入研究。

Objective To compare dual-color in-situ hybridization （DISH） with fluorescence in situ hybridization（FISH） in evaluating the human HER2 gene status in invasive breast cancer. Methods HER2 gene status in 110 cases of breast invasive ductal carcinomas with a 2 ＋ score on immunohistochemistry （IHC） was investigated by FISH and DISH. The 2007 and 2013 ASCO （American Society of Clinical Oncology）/CAP （College of American Pathologists ） HER2 guideline were used respectively to evaluate the agreement between these two techniques. Results （ 1 ） Using the 2007 ASCO/ CAP guideline, the overall concordance between FISH and DISH was 97.3 % （107/110）. Fifty of 51 samples with amplification by FISH were also detected by DISH and the remaining one sample was equivocal. Eight of l0 equivocal samples by FISH were equivocal by DISH and the remaining two samples were negative. Forty- nine samples with no amplification by FISH were all negative by DISH. The concordance was 98.0% , 8/10 and 100. 0% respectively for the FISH positive, equivocal and negative groups. （2） Using the 2013 ASCO/ CAP guideline, the overall concordance between FISH and DISH was 90. 0% （99/110）. Fifty-three of 55 samples with amplification by FISH were also detected by DISH and the remaining two were equivocal and negative respectively. Two of 12 equivocal samples by FISH were equivocal by DISH and the remaining ten samples were negative in 7 cases and equivocal in 3 cases. Forty-three samples with no amplification by FISH were all negative by DISH. The concordance was 96. 4% , 3/12 and 100. 0% respectively for the FISH positive, equivocal and negative groups. Pearson correlation analysis indicated that the HER2 status detected by FISH and DISH were significantly correlated with each other （R = 0. 584, P 〈0. 01 ）. ConclusionsThere is a high concordance between DISH and FISH for assessing the HER2 gene status in invasive breast cancer. DISH is a new option for assessing HER2 gene status of breast cancer in clinical practice. The clinical significance of the discordance between DISH and FISH in equivocal cases warrants further study.