Bethune Gillian C, Pettit Alexandra S L, Veldhuijzen van Zanten Daniel, Barnes Penelope J
Department of Pathology and Laboratory Medicine, Nova Scotia Health Authority and Dalhousie University, Halifax, Nova Scotia, Canada.
Histopathology. 2017 May;70(6):966-974. doi: 10.1111/his.13160. Epub 2017 Feb 24.
The 2013 American Society of Clinical Oncology and the College of American Pathologists (ASCO/CAP) HER2 guidelines recommend testing all invasive breast cancers for HER2, typically with immunohistochemistry (IHC) followed by in-situ hybridization (ISH) when IHC is equivocal. As well-differentiated breast cancers are rarely HER2-positive, we assessed the value of routine reflex HER2 ISH testing for this subset of breast cancers.
We collected HER2 IHC 2+ cases and fluorescence in-situ hybridization (FISH) data from primary breast cancers with well-differentiated tumour types (grade 1 ductal carcinomas, classic lobular carcinomas, tubular, cribriform and pure mucinous carcinomas) at our centre from 2010 to 2015. Haematoxylin and eosin (H&E) and IHC slides were reviewed to confirm tumour type, grade and IHC score based on ASCO/CAP 2013 guidelines and their recent revisions. Of 4633 invasive carcinomas, 1133 had a well-differentiated tumour type; 177 of these were HER2 IHC equivocal, three of which were low-level amplified by FISH (0.3% of all well-differentiated tumours). One amplified case was classic invasive lobular carcinoma and two were invasive ductal carcinomas, grade 1. One amplified case had chromosome 17 monosomy, and one was rescored as HER2 IHC 1+ upon review. 'Basolateral' staining was noted in one amplified case and in 65 of 174 (37.4%) non-amplified cases. This incomplete membranous staining pattern was observed in the majority of invasive ductal carcinomas that were rescored as 1+ according to the revised 2013 guidelines.
The rate of HER2 amplification among well-differentiated breast cancers is very low. Basolateral staining in well-differentiated tumours may be overinterpreted as HER2 IHC 2+, but is rarely associated with HER2 amplification.
2013年美国临床肿瘤学会和美国病理学家学会（ASCO/CAP）的HER2指南建议对所有浸润性乳腺癌进行HER2检测，通常采用免疫组织化学（IHC）方法，当IHC结果不明确时再进行原位杂交（ISH）检测。由于高分化乳腺癌很少为HER2阳性，我们评估了对这一亚组乳腺癌进行常规HER2 ISH检测的价值。
我们收集了2010年至2015年在本中心诊断的高分化肿瘤类型（1级导管癌、经典小叶癌、管状癌、筛状癌和纯黏液癌）的原发性乳腺癌的HER2 IHC 2+病例及荧光原位杂交（FISH）数据。苏木精和伊红（H&E）染色切片及IHC切片经复查，以根据ASCO/CAP 2013指南及其最新修订版确认肿瘤类型、分级及IHC评分。在4633例浸润性癌中，1133例为高分化肿瘤类型；其中177例HER2 IHC结果不明确，其中3例经FISH检测为低水平扩增（占所有高分化肿瘤的0.3%）。1例扩增病例为经典浸润性小叶癌，2例为1级浸润性导管癌。1例扩增病例存在17号染色体单体，1例经复查重新评分为HER2 IHC 1+。1例扩增病例及174例非扩增病例中的65例（37.4%）观察到“基底外侧”染色。根据2013年修订指南重新评分为1+的大多数浸润性导管癌中均观察到这种不完全的膜染色模式。
高分化乳腺癌中HER2扩增率非常低。高分化肿瘤中的基底外侧染色可能被过度解读为HER2 IHC 2+阳性，但很少与HER2扩增相关。
