Killeen Jeffrey L, Ortega-Lopez Anna, Shaha James, Shaha Steven H, Fu Jennifer B
Department of Pathology, Kapiolani Medical Center for Women and Children, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii 96826, USA.
Breast Cancer Res Treat. 2006 Jul;98(1):99-108. doi: 10.1007/s10549-005-9136-1. Epub 2006 Mar 15.
The significance of HER-2/neu results obtained by immunohistochemical analyses (IHC) which are neither negative nor strongly positive is controversial. The incidence of fluorescence in situ hybridization (FISH) positivity in these tumors is small and the implication is that these borderline results represent laboratory misclassification. We analyzed the tumor characteristics of these HER-2/neu borderline tumors to determine if they represent a unique tumor type.
HER-2/neu status was determined by image analysis (IA) of IHC sections in 669 cases of invasive breast cancer. Borderline cases were reflexed to FISH to determine gene status. HER-2/neu results were compared to tumor morphology and other tumor markers.
HER-2/neu was negative, borderline and positive in 69.5, 15.8, and 14.6% of cases, respectively. HER-2/neu amplification was present in 17.3% of borderline cases. The borderline group is significantly different from the HER-2/neu positive group for all parameters studied except Ki-67. Compared to the HER-2/neu negative group, the borderline group showed a significantly higher HER-2/neu gene copy number and a trend towards lower progesterone receptor expression (p=0.058). Compared to the HER-2/neu negative group, the HER-2/neu borderline/FISH-negative group showed significantly lower PR expression. Compared to the HER-2/neu positive group, the HER-2/neu borderline/FISH positive group showed significant differences with multiple parameters.
Borderline HER-2/neu tumors are a unique tumor type and do not represent laboratory imprecision. Hormone receptor alterations are associated with early changes in HER-2/neu expression. While IA is capable of detecting these changes, current FISH methodology is not.
通过免疫组织化学分析（IHC）获得的既非阴性也非强阳性的HER-2/neu结果的意义存在争议。这些肿瘤中荧光原位杂交（FISH）阳性的发生率较低，这意味着这些临界结果代表实验室分类错误。我们分析了这些HER-2/neu临界肿瘤的肿瘤特征，以确定它们是否代表一种独特的肿瘤类型。
通过对669例浸润性乳腺癌的IHC切片进行图像分析（IA）来确定HER-2/neu状态。临界病例进行FISH检测以确定基因状态。将HER-2/neu结果与肿瘤形态和其他肿瘤标志物进行比较。
HER-2/neu阴性、临界和阳性病例分别占69.5%、15.8%和14.6%。17.3%的临界病例存在HER-2/neu扩增。除Ki-67外，临界组与HER-2/neu阳性组在所有研究参数上均有显著差异。与HER-2/neu阴性组相比，临界组显示出显著更高的HER-2/neu基因拷贝数，且孕激素受体表达有降低趋势（p=0.058）。与HER-2/neu阴性组相比，HER-2/neu临界/FISH阴性组显示PR表达显著降低。与HER-2/neu阳性组相比，HER-2/neu临界/FISH阳性组在多个参数上存在显著差异。
HER-2/neu临界肿瘤是一种独特的肿瘤类型，并非代表实验室不精确。激素受体改变与HER-2/neu表达的早期变化相关。虽然IA能够检测到这些变化，但目前的FISH方法却不能。
