Comparative Evaluation of High-Throughput Small-Core (0.6-mm) and Large-Core (2-mm) Thyroid Tissue Microarray: Is Larger Better?

Abstract

Context.—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. Objective.—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. Design.—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. Results.—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%). Conclusion.—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.