Institute of Medicine, Chung-Shan Medical University, Taichung, Taiwan; Department of Pathology, Chung-Shan Medical University and Chung Shan Medical University Hospital, Taichung, Taiwan.
Department of Statistics and Informatics Science, Providence University, Taichung, Taiwan.
Hum Pathol. 2014 Apr;45(4):810-6. doi: 10.1016/j.humpath.2013.11.016. Epub 2013 Dec 12.
HER2 gene amplification and protein over-expression are important factors in predicting clinical sensitivity to anti-HER2 therapies in breast, gastric or gastroesophageal junction cancer patients. The aim of this study was to evaluate the correlation between HER2 gene copy numbers and HER2 protein expressions in mucinous epithelial ovarian cancer (EOC). Of the 49 tissue microarray samples of mucinous EOC, we applied 2010 ToGA trial (Trastuzumab for Gastric Cancer) surgical specimen scoring criteria to analyze the HER2 protein expression by an immunohistochemistry (IHC) test with Dako (Carpenteria, CA), c-erb-B2 antibody, and the HER2 gene amplification by the fluorescence in situ hybridization (FISH) test with Abbott/Vysis PathVysion HER2 DNA Probe Kit (Abbott Molecular Inc., Des Plaines, IA). We achieved a high overall concordance of 97.56% between nonequivocal HER2 results by IHC and FISH tests. In addition, HER2 gene copies before chromosome-17 correction increased significantly in a stepwise order through the negative, equivocal and positive IHC result categories (P<.001), as did the HER2 gene copies after chromosome-17 correction (P<.001). On the other hand, HER2 IHC results correlated significantly with both chromosome-17-uncorrected HER2 gene copy numbers (ρ=0.630, P<.001) and chromosome-17 corrected HER2 gene copy numbers (ρ=0.558, P<.001). We concluded that both chromosome-17 corrected and uncorrected HER2 gene copies correlated significantly with HER2 IHC results. Tests for the HER2 gene copies per tumor cell either before or after correction of chromosome-17 can be applied as a potentially valuable tool to analyze the HER2 status in mucinous EOC.
HER2 基因扩增和蛋白过表达是预测乳腺癌、胃癌或胃食管交界部癌患者对抗 HER2 治疗临床敏感性的重要因素。本研究旨在评估黏液性卵巢上皮癌（EOC）中 HER2 基因拷贝数与 HER2 蛋白表达之间的相关性。在 49 例黏液性 EOC 的组织微阵列样本中，我们应用 2010 年 ToGA 试验（曲妥珠单抗治疗胃癌）手术标本评分标准，通过免疫组织化学（IHC）试验（Dako，加利福尼亚州卡彭特里亚）和 c-erb-B2 抗体分析 HER2 蛋白表达，并通过荧光原位杂交（FISH）试验（雅培/ Vysis PathVysion HER2 DNA 探针试剂盒，雅培分子公司，德斯普兰斯，IA）分析 HER2 基因扩增。IHC 和 FISH 试验的结果具有很高的一致性，达到 97.56%。此外，在经过染色体 17 校正后，HER2 基因拷贝数在阴性、不确定和阳性 IHC 结果分类中呈逐步递增趋势（P<.001），未经染色体 17 校正的 HER2 基因拷贝数也呈递增趋势（P<.001）。另一方面，HER2 IHC 结果与未经染色体 17 校正的 HER2 基因拷贝数（ρ=0.630，P<.001）和校正后的 HER2 基因拷贝数（ρ=0.558，P<.001）均呈显著相关。我们得出结论，未经染色体 17 校正和校正后的 HER2 基因拷贝数均与 HER2 IHC 结果显著相关。在未经染色体 17 校正或校正后，对每个肿瘤细胞的 HER2 基因拷贝数进行检测，可以作为分析黏液性 EOC 中 HER2 状态的一种有价值的工具。
