HER2过表达与基因扩增的相关性及其与17号染色体非整倍体的关系：5年浸润性导管癌和小叶癌的经验
Correlation of HER2 overexpression with gene amplification and its relation to chromosome 17 aneuploidy: a 5-year experience with invasive ductal and lobular carcinomas.
作者信息
Nassar Aziza, Khoor Andras, Radhakrishnan Reshmitha, Radhakrishnan Anu, Cohen Cynthia
机构信息
Division of Anatomic Pathology, Mayo Clinic Jacksonville, Florida.
Cornell University School of Medicine Ithaca, New York.
出版信息
Int J Clin Exp Pathol. 2014 Aug 15;7(9):6254-61. eCollection 2014.
The HER2 oncogene shows expression or amplification, or both, in approximately 15% to 20% of breast cancers and has been associated with poor prognosis and a response to trastuzumab therapy. HER2 gene status determines the eligibility of breast cancer patients for trastuzumab therapy and a large fraction (41-56%) of these patients respond to targeted therapy. Several studies have related the increased expression of HER2 to an increased copy number of chromosome 17, rather than amplification of the HER2 gene. We compared the results of immunohistochemistry and fluorescence in situ hybridization in both invasive ductal and invasive lobular carcinomas, to determine the frequency of chromosome 17 aneuploidy associated with discordant results. In total, 390 invasive ductal carcinomas and 180 invasive lobular carcinomas diagnosed from January 2000 to December 2005 were included in the study only if results were available for immunohistochemistry (HercepTest; DAKO, Carpinteria, California) and fluorescence in situ hybridization (PathVysion HER2 DNA Probe Kit; Abbott Laboratories, Des Plaines, Illinois). Tumors classified as invasive ductal carcinomas were graded according to the Bloom-Richardson grading system. Correlation between the results of immunohistochemistry and fluorescence in situ hybridization was performed for all categories. Among invasive ductal carcinomas, 29% (115/390) showed chromosome 17 aneuploidy, mostly associated with grade 3/HER2 2+ (45%) or grade 2/HER2 3+ (55%) that were not amplified. Also, 34% (12/35) of invasive lobular carcinomas showed chromosome 17 aneuploidy; approximately one-third of these cases were HER2 2+ (33%) and HER2 3+ (37%) that were not amplified. Discordance between the results of immunohistochemistry and fluorescence in situ hybridization in both ductal and lobular carcinomas is largely associated with chromosome 17 aneuploidy.
HER2癌基因在约15%至20%的乳腺癌中出现表达或扩增，或两者皆有，并且与预后不良及对曲妥珠单抗治疗的反应相关。HER2基因状态决定了乳腺癌患者是否适合接受曲妥珠单抗治疗，其中很大一部分（41 - 56%）患者对靶向治疗有反应。多项研究已将HER2表达增加与17号染色体拷贝数增加相关联，而非HER2基因扩增。我们比较了浸润性导管癌和浸润性小叶癌中免疫组织化学和荧光原位杂交的结果，以确定与结果不一致相关的17号染色体非整倍体频率。总共纳入了2000年1月至2005年12月诊断的390例浸润性导管癌和180例浸润性小叶癌，前提是有免疫组织化学（HercepTest；DAKO，加利福尼亚州卡平特里亚）和荧光原位杂交（PathVysion HER2 DNA探针试剂盒；雅培实验室，伊利诺伊州德斯普兰斯）的结果。分类为浸润性导管癌的肿瘤根据Bloom - Richardson分级系统进行分级。对所有类别进行免疫组织化学和荧光原位杂交结果之间的相关性分析。在浸润性导管癌中，29%（115/390）显示17号染色体非整倍体，主要与未扩增的3级/HER2 2 +（45%）或2级/HER2 3 +（55%）相关。此外，34%（12/35）的浸润性小叶癌显示17号染色体非整倍体；这些病例中约三分之一为未扩增的HER2 2 +（33%）和HER2 3 +（37%）。导管癌和小叶癌中免疫组织化学与荧光原位杂交结果之间的不一致在很大程度上与17号染色体非整倍体相关。
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