Oyama Tetsunari, Ishikawa Yuko, Hayashi Mitsuhiroi, Arihiro Kohji, Horiguchi Jun
Department of Pathology, Dokkyo Medical School of Medicine, Japan.
Breast Cancer. 2007;14(2):182-8. doi: 10.2325/jbcs.976.
A task force of the Japanese Breast Cancer Society has proposed a recommendation for adequate evaluation of hormone receptors in routine practice, in order to standardize handling of tissues, staining techniques and scoring systems. As a part of the study, several examinations were conducted to detect the effect of technical problems, including the influence of fixation time and other fixation and processing conditions, on the immunoreactivity for ERalpha. There is little influence of prolonged fixation on the immunoreactivity for ERalpha, except for cases in which particularly over-fixed blocks are used. A delay in the onset of fixation could decrease the immunohistochemical findings of steroid receptors, compared with shorter or longer fixation, and the situation is similar to the fixation of a whole large surgical specimen in formalin in a big bucket. Incomplete fixation might be an important cause of heterogeneiety of immunoreactivity for ERalpha. Manual and automated immunohistochemical (IHC) staining by DAKO (Glostrup, Denmark) and Biogenex (San Ramon, CA) and automated IHC staining by Ventana Medical Systems (Tucson, AZ) each employ different methods. Using a scoring system, in which the proportion of cells stained in each specimen was recorded as 0, less than 1%, 1% or more and less than 10%, and 10% or more, the intermethod variability of those IHC staining methods exhibited substantial multi-rater kappa values concerning the ER and PgR (kappa for ER according to the percentage of positive cells=0.67; PgR=0.72). Concerning intermethod consistency, the scoring system based on the percentage of positive cells was advantageous over other scoring systems, based on the intensity of nuclear staining. Using double staining, patients with ER-positive and HER2-positive tumors can be classified as those with co-expressed tumors and those with differently expressed tumors. As such, the co-expressed tumor might be resistant to antiestrogen therapy in ERalpha-positive and HER2-positive breast cancer and double staining might lead to the development of new therapeutic strategies for hormone and HER2-positive breast cancer.
日本乳腺癌协会的一个特别工作组提出了一项建议，旨在规范日常实践中激素受体的评估，以实现组织处理、染色技术和评分系统的标准化。作为该研究的一部分，进行了多项检查，以检测包括固定时间及其他固定和处理条件在内的技术问题对雌激素受体α（ERα）免疫反应性的影响。除了使用过度固定的组织块的情况外，延长固定时间对ERα免疫反应性影响很小。与较短或较长时间的固定相比，固定延迟可能会降低类固醇受体的免疫组化结果，这种情况类似于将整个大手术标本放在大桶中的福尔马林里固定。固定不完全可能是ERα免疫反应性异质性的一个重要原因。丹麦格洛斯楚普的达科公司、美国加利福尼亚州圣拉蒙的生物基因公司的手动和自动免疫组化（IHC）染色，以及美国亚利桑那州图森的文塔纳医疗系统公司的自动IHC染色，各自采用不同的方法。使用一种评分系统，将每个标本中染色细胞的比例记录为0、小于1%、1%及以上且小于10%、10%及以上，这些IHC染色方法的方法间变异性在ER和孕激素受体（PgR）方面表现出显著的多评估者kappa值（根据阳性细胞百分比计算的ER的kappa值 = 0.67；PgR = 0.72）。关于方法间的一致性，基于阳性细胞百分比的评分系统比基于细胞核染色强度的其他评分系统更具优势。使用双重染色，ER阳性和HER2阳性肿瘤患者可分为共表达肿瘤患者和差异表达肿瘤患者。因此，共表达肿瘤可能对ERα阳性和HER2阳性乳腺癌的抗雌激素治疗耐药，双重染色可能会为激素和HER2阳性乳腺癌开发新的治疗策略。
