Fergenbaum Jennifer H, Garcia-Closas Montserrat, Hewitt Stephen M, Lissowska Jolanta, Sakoda Lori C, Sherman Mark E
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health/DHHS, 6120 Executive Boulevard, Executive Plaza South, Room 7080, Rockville, MD 20852, USA.
Cancer Epidemiol Biomarkers Prev. 2004 Apr;13(4):667-72.
Immunohistochemical characterization of tumor tissues in epidemiological studies is a promising approach to identify breast cancer subtypes with distinct etiology. The recent development of the tissue microarray (TMA) technique allows for standardized, rapid, and cost-effective immunohistochemical characterization of many cases, which is critical in epidemiological studies. Sectioning paraffin blocks at different times results in loss of material, which can be reduced by preparing many sections each time a block is cut. However, data suggest that staining intensity declines in whole sections prepared from conventional paraffin blocks with storage time, resulting in false-negative results. This problem would be accentuated in TMAs because of the limited tissue representation of each case. To evaluate this concern, we prepared a single TMA block from 125 invasive breast carcinomas collected in a population-based case-control study conducted in Poland and compared estrogen receptor (ER-alpha), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression in sections cut and stored for 6 months at room temperature with sections cut from the same TMA block and stained on the same day. Percentage of positive cases for stored versus fresh sections was similar for ER (59.0%) but significantly higher in fresh sections for PR (56.3% versus 64.1%, P = 0.01) and HER2 (45.5% versus 64.4%, P < 0.001). Among cases positive in both stored and fresh sections, the median percentage of immunoreactive cells was significantly reduced and the staining intensity was consistently lower in stored compared with fresh sections. We conclude that loss of immunoreactivity is an important problem in TMAs of breast cancer. Improved methods for sectioning TMAs and storing tissue sections aimed at reducing loss of immunoreactivity are critical for the use of TMAs in epidemiological studies.
在流行病学研究中，对肿瘤组织进行免疫组织化学特征分析是识别具有不同病因的乳腺癌亚型的一种有前景的方法。组织微阵列（TMA）技术的最新发展使得对许多病例进行标准化、快速且经济高效的免疫组织化学特征分析成为可能，这在流行病学研究中至关重要。在不同时间对石蜡块进行切片会导致材料损失，每次切割石蜡块时制备多个切片可减少这种损失。然而，数据表明，从传统石蜡块制备的全切片中，染色强度会随着储存时间而下降，从而导致假阴性结果。由于每个病例在TMA中的组织代表性有限，这个问题在TMA中会更加突出。为了评估这一问题，我们从波兰一项基于人群的病例对照研究中收集的125例浸润性乳腺癌中制备了一个单一的TMA块，并比较了在室温下切割并储存6个月的切片与从同一TMA块切割并在同一天染色的切片中雌激素受体（ER-α）、孕激素受体（PR）和人表皮生长因子受体2（HER2）的表达情况。储存切片与新鲜切片的阳性病例百分比对于ER相似（59.0%），但PR在新鲜切片中的阳性率显著更高（56.3%对64.1%，P = 0.01），HER2也是如此（45.5%对64.4%，P < 0.001）。在储存切片和新鲜切片中均为阳性的病例中，与新鲜切片相比，储存切片中免疫反应性细胞的中位数百分比显著降低，且染色强度始终较低。我们得出结论，免疫反应性丧失是乳腺癌TMA中的一个重要问题。改进TMA切片和组织切片储存方法以减少免疫反应性丧失对于在流行病学研究中使用TMA至关重要。
