摘要目的 探讨HER2 免疫组织化学( IHC) 1+乳腺癌患者的基因扩增状态和原位HER2 mRNA表达情况,为精准检测HER2及相关临床策略的修订提供初步参考数据.方法 抽取北京协和医院2011至2013年间手术获取的非特殊型浸润性乳腺癌HER2 IHC 1+存档蜡块标本65例,制作组织芯片,分别采用荧光原位杂交(FISH)和RNAscope方法检测其HER2基因状态和原位mRNA表达水平.如原发灶HER2的FISH结果不确定或阴性但mRNA高表达,再以FISH复检其淋巴结转移灶的HER2基因状态.结果 在65例标本中,FISH阳性4例( 6.2%),其中2例为HER2/CEP17＞2且平均HER2基因拷贝数＞4,另2例为HER2/CEP17＜2但平均HER2基因拷贝数＞6;在此4例FISH阳性标本中,2例为mRNA高表达(RNAscope 3分),另2例为中度表达(RNAscope 2分).另外,在全部标本中,3例HER2/CEP17＞2但平均HER2基因拷贝数＜4,其中2例mRNA高表达(RNAscope 3分和4分),另1例mRNA中度表达( RNAscope 2分).未见HER2基因状态及mRNA表达与临床病理特征(肿瘤大小、分化程度、淋巴结转移、脉管癌栓)之间存在明显相关性( P均＞0.05).结论 在本组HER2 IHC 1+乳腺癌中检出了部分FISH阳性的标本,其mRNA也有一定程度的表达,可判断为抗HER2治疗的潜在获益者.鉴于精准分子分型对于乳腺癌临床处理及相关诊疗策略制定具有重要意义,后续有必要进行大样本量的验证.

abstractsObjective To investigate human epidermal growth factor 2 (HER2) gene status and in situ mRNA expression in breast cancers with immunohistochemistry( IHC) 1+,and to reveal HER2 positive rate in these patients to provide reference data for obtaining precise HER2 results and modifying relevant clinical strategy to breast cancer. Methods Sixty-five IHC 1+ formalin-fixed and paraffin-embedded samples of invasive breast carcinoma of no special type ( IBC-NST) were collected by surgical operation at Peking Union Medical College Hospital during 2011 to 2013. HER2 status and in situ mRNA expression were tested by fluorescence in situ hybridization ( FISH) and RNAscope, respectively, by using tissue microarray. Metastatic lymph node was re-tested by FISH if HER2 status was equivocal or negative and with high expression of mRNA in the primary lesion. Results Four of 65 samples (6.2%) were FISH positive, which included 2 cases of HER2/CEP17＞2 and average HER2 copy number＞4 and 2 cases of HER2/CEP17＜2 and average HER2 copy number＞6. In the 4 samples of HER2 positive, 2 patients showed high in situ mRNA expression (3 scores by RNAscope), 2 patients showed moderate in situ mRNA expression (2 scores by RNAscope). In addition, 3 specimens with HER2/CEP17＞2 and average HER2 copy number＜4 were found in all patients, which included 2 cases of high in situ mRNA expression ( 3 and 4 scores by RNAscope) and 1 cases of moderate in situ mRNA expression ( 2 scores by RNAscope). There was no significant association between HER2 status or mRNA expression and clinicopathological characteristics, including tumor size, histopathological differentiation, lymph node metastasis and lymphovascular invasion (P＞0.05).Conclusions A small number of HER2 IHC 1+patients exist mRNA expression by using FISH method, which suggested that these patients might benefit from anti-HER2 therapy potentially. Since the importance for patients with breast cancers to develop diagnostic and therapeutic strategies from accurate molecular typing, further studies based on a larger cohort are needed to validate our findings.