Department of Pathology, Ohio State University Medical Center, Columbus, USA.
Arch Pathol Lab Med. 2012 Feb;136(2):199-203. doi: 10.5858/arpa.2011-0080-OA.
Tissue microarrays (TMAs) are useful in gene/protein expression profiling of large number of tumors. Several studies have validated that a 0.6-mm core of a large tumor would give results similar to results of the whole section. However, cores from colloid-filled thyroid follicles, for example in breast carcinoma, may contain fewer cells compared to solid tumors.
The aim of this study is to validate thyroid TMAs choosing 2 core diameters, 0.6 and 2 mm, and to study the effect of core size and grid density on concordance with whole sections.
0.6-mm tissue cores were arrayed on a high-density TMA (406 cores). Two low-density TMAs (35 cores each) composed of 2-mm cores were also constructed. Immunohistochemistry was performed using primary antibodies to cytokeratin 19, HBME1, and CITED1 that have been found to be useful in the diagnosis of thyroid carcinoma. The results were compared with whole sections.
The concordance between high-density TMAs and whole sections was 61 of 77 (79%) for cytokeratin 19; 76 of 80 (95%) for HBME 1; and 67 of 75 (89%) for CITED1. The concordance between the low-density TMAs and whole sections was cytokeratin 19, 41 of 51 (80%) for cytokeratin 19; HBME1, 52 of 56 (92.8%) for HBME1 and 58 of 59 (98%) for CITED1. The most frequent discordance was negative core but positive focal heterogeneous protein expression in whole sections. On whole sections, the sensitivity of tests increased but the specificity decreased compared to TMAs; however, the accuracy remained similar (77%-83%).
Focal and heterogeneous protein expression was the most frequent reason for false negative results in TMAs. Tissue microarray remains an accurate method of screening for protein expression in a large number of thyroid tissues irrespective of core diameters or grid densities.
组织微阵列（TMA）在大量肿瘤的基因/蛋白质表达谱分析中非常有用。多项研究已经验证，大肿瘤的 0.6 毫米核心可以提供与整个切片相似的结果。然而，例如在乳腺癌中充满胶体的甲状腺滤泡的核心可能包含比实体瘤更少的细胞。
本研究旨在验证甲状腺 TMA，选择 0.6 和 2 毫米两种核心直径，并研究核心大小和网格密度对与全切片一致性的影响。
将 0.6 毫米的组织芯排列在高密度 TMA（406 个芯）上。还构建了两个由 2 毫米芯组成的低密度 TMA（每个 35 个芯）。使用已发现对甲状腺癌诊断有用的细胞角蛋白 19、HBME1 和 CITED1 的主要抗体进行免疫组织化学染色。将结果与全切片进行比较。
高密度 TMA 与全切片的一致性为细胞角蛋白 19 为 77 个中的 61 个（79%）；HBME1 为 80 个中的 76 个（95%）；CITED1 为 75 个中的 67 个（89%）。低密度 TMA 与全切片的一致性为细胞角蛋白 19 为 51 个中的 41 个（80%）；HBME1 为 56 个中的 52 个（92.8%）；CITED1 为 59 个中的 58 个（98%）。最常见的不匹配是核心阴性但全切片出现阳性局灶性异质蛋白表达。与 TMA 相比，全切片上测试的敏感性增加，但特异性降低；然而，准确性仍然相似（77%-83%）。
局灶性和异质性蛋白表达是 TMA 中假阴性结果最常见的原因。组织微阵列仍然是一种准确的方法，可用于筛选大量甲状腺组织中的蛋白质表达，无论核心直径或网格密度如何。
