Validation of tissue microarrays for immunohistochemical profiling of cancer specimens using the example of human fibroblastic tumors

Tissue microarrays allow high-throughput molecular profiling of cancer spec imens by immunohistochemistry. Phenotype information of sections from array ed biopsies on a multitissue block needs to be representative of full secti ons, as protein expression varies throughout the entire tumor specimen. To validate the use of tissue microarrays for immunophenotyping, we studied a group of 59 fibroblastic tumors with variable protein expression patterns b y immunohistochemistry for Ki-67, p53, and the retinoblastoma protein (pRB) , Data on full tissue sections were compared to the results of one, two, an d three 0.6-mm core biopsies per tumor on a tissue array. Ki-67 and p53 sta ining was read as two categories (positive or negative). Concordance for th is staining between tissue arrays with triplicate cores per tumor and full sections were 96 and 98%, respectively. For pRB staining was read as three categories thigh, moderate, or negative), where concordance was 91%, The us e of three cores per tumor resulted in lower numbers of lost cases and lowe r nonconcordance with standard full sections as compared to one or two core s per tumor. Correlations between phenotypes and clinical outcome were not significantly different between full section and array-based analysis, Trip licate 0.6-mm core biopsies sampled on tissue arrays provide a reliable sys tem for high-throughput expression profiling by immunohistochemistry when c ompared to standard full sections. Triplicate cores offer a higher rate of assessable cases and a lower rate of nonconcordant readings than one or two cores. Concordance of triplicate cores is high (96 to 98%) for two categor y distinction and decreases with the complexity of the phenotypes being ana lyzed (91%).