伴17号染色体多体的乳腺癌患者人表皮生长因子受体2状态的评估及意义

Assessment and significance of human epidermal growth factor receptor 2 gene status in breast cancer with polysomy of chromosome 17

目的探讨乳腺癌17号染色体多体（多体17）对人表皮生长因子受体2（HER2）状态评估的影响及意义。方法收集338例行HER2免疫组织化学（IHC）及荧光原位杂交（FISH）检测的乳腺癌患者临床病理资料，根据2013年美国临床肿瘤学会／美国病理医师学院（ASCO／CAP）乳腺癌HER2检测指南标准，分析17号染色体中间着丝粒区（CEP17）拷贝数及多体17对HER2评估的影响，并分析多体17与乳腺癌患者临床病理特征的关系。结果338例乳腺癌患者中，HER2IHC阴性9例（2．7％），不确定309例（91．4％），阳性20例（5．9％）。HER2FISH阴性226例（66．9％），不确定13例（3．8％），阳性99例（29．3％）。338例乳腺癌患者中，42例（12．4％）为多体17，291例（86．1％）为17号染色体双体，5例（1．5％）为17号染色体单体。多体17与HER2蛋白表达有关（P=0．046）。多体17患者的HER2FISH结果和HER2拷贝数与非多体17患者比较，差异有统计学意义（P〈0．001）。多体17患者的HER2／CEP17比值与非多体17患者比较，差异无统计学意义（P=0．930）。多体17的存在与乳腺癌病理学分级和Ki-67指数有关（均P〈0．05），而与患者年龄、肿瘤大小、淋巴结转移、雌激素受体（ER）状态、孕激素受体（PR）状态和新辅助疗效评估无关（均P〉0．05）。结论在多体17的乳腺癌中评估HER2信号的绝对拷贝数尤为重要，并应结合HER2／CEP17比值及HER2蛋白表达水平进行综合评估。

Objective To explore the impact of polysomy of chromosome 17 on the interpretation of human epidermal growth factor receptor 2 （HER2） status and its clinical significance in breast cancers. Methods Clincopathological data of 338 breast cancer patients were collected, and the association of clinieopathological characteristics with polysomy of chromosome 17 was analyzed. Based on the American Society of Clinical Ontology/College of American Pathologists updated recommendations of HER2 testing in breast cancer in 2013, the relationships between the copy number of centromeres on chromosome 17 （CEP17） and HER2 status, other important biological markers and clincopathological features of breast cancer were analyzed statistically. Results Immunohistochemical examination revealed that among the 338 breast cancer cases, there were 9 （2.7%） HER2-negative cases, 309 （91.4%） HER2-equivoeal cases, and 20 （5.9%） HER2-positive cases. The FISH analysis showed that there were 226 （66.9%） HER2-negative cases, 13 （3.8%） HER2-equivocal cases, and 99 （ 29.3% ） HER2-positive cases. Among the 338 breast cancer patients, 42 （12.4%） eases were identified as chromosome 17 polysomy （polysomy 17）, 291 （86.1%） cases were chromosome 17 disomy, and 5 （1.3%） eases were chromosome 17 monosomy. Polysomy 17 showed significant correlation with the intensity of HER2 protein expression （P = 0.046 ）. The HER2 FISH results and HER2 gene copy＇number of polysomy 17 cases showed significant differences from the non- polysomy 17 cases （P〈0.001）. There were no significant differences of HER2/CEP17 ratio between the polysomy 17 and non-polysomy 17 groups （P=0.930）. Polysomy 17 cases showed a significant relationship with tumor grading and Ki-67 index （P〈0.05）, but not with the age of patient, tumor size, lymph node metastasis, ER and PR expressions, and effect evaluation of neoadjuvant chemotherapy （P 〉 0.05 ）. Conclusions In the breast cancer with polysomy of chromosome 17, assessment of the absolute copy number of HER2 signals is even more important, and the HER2/CEP17 ratio and HER2 protein expression levels should be comprehensively evaluated together.