Evolving Practices of Diagnostic Immunohistochemistry

It has been more than 6 years since the Archives of Pathology & Laboratory Medicine published the special issue on diagnostic immunohistochemistry (IHC) consisting of a series of review articles edited by Jaishree Jagirdar, MD, which was a great, concise, and yet comprehensive review and update on important IHC markers, panels, and diagnostic strategies. It has been my great honor and immense privilege to organize this new special issue on IHC, contributed to by pathologists from Geisinger Medical Center (Danville, Pennsylvania) and many expert pathologists from others medical centers. This 2-part special issue features 14 review articles with an attempt to cover IHC automation, standardization of diagnostic IHC, and the role of IHC in diagnosing tumors in major organs and tumors of unknown primary. This series begins with an article emphasizing standardization of diagnostic IHC in the preanalytic, analytic, and postanalytic phases, with a specific focus on (1) newly proposed guidelines on antibody validation from the College of American Pathologists Pathology and Laboratory Quality Center, (2) testing/optimizing a new antibody and troubleshooting, (3) interpreting and reporting IHC assay results, (4) continuing quality improvement programs, and (5) developing and implementing the concept of best practices in IHC. When it comes to the question of how to implement best practices, emphasis is placed on the evidence-based application of IHC markers to practical scenarios, which includes eliminating unnecessary markers, starting with a small IHC panel and continuing with a second panel only when the first panel leads to an inconclusive result. Two questions should be asked before ordering any IHC assay: ‘‘Why should I order this marker?’’ and ‘‘Does it change my diagnosis and patient care?’’ In addition, some external quality control programs and College of American Pathologists checklists for inspecting a clinical IHC laboratory are outlined. The role of digital pathology in the field of diagnostic IHC is briefly discussed as well. The second review article compares and contrasts the recent technological advances in new generation automated IHC platforms from all major companies. Some advantages over the prior automated platforms are stressed, including complete walkaway automation, faster speed, use of less reagents, user friendliness, better integration with laboratory information systems, effective waste control, capability for multiplexing, and more reliable and reproducible results. One of the most frequent and important applications of diagnostic IHC is to assist in working up an undifferentiated neoplasm/tumor of uncertain primary site. The third review article comprehensively reviews some diagnostic strategies and algorithms, updates many recently described diagnostic markers such as GATA binding protein 3 (GATA3), placental S100 (S100P), mammary serine protease inhibitor (maspin), von Hippel-Lindau tumor suppressor gene protein (pVHL), paired box gene (PAX) 8, ETS-related gene (ERG), sal-like protein 4 (SALL4), sex-determining region Y box (SOX) 10, arginase-1, napsin A, special AT-rich sequence-binding protein 2 (SATB2), and cadherin-17, and refines the diagnostic IHC panels frequently used in daily practice. The remaining 11 review articles are devoted to organspecific diagnostic IHC. In the lung and pleural review article, p40, desmoglein-3, desmocollin-3, and cytokeratin (CK) 5 are described as the most effective panel of IHC markers for squamous cell carcinoma; hepatocyte nuclear factor 4 a (HNF4a) is demonstrated to be a marker for invasive mucinous adenocarcinoma of the lung; and glucose transporter 1 (Glut1), insulin-like growth factor II messenger RNA–binding protein (IMP3), and cluster of differentiation (CD) 146 are shown to be helpful in differentiating reactive conditions from malignant mesothelial proliferations. In breast pathology, GATA3 has been reported in several publications to be expressed in most breast ductal and lobular carcinomas, including more than 50% of ERnegative breast carcinomas and metaplastic carcinomas. Ankyrin repeat domain 30A (NY-BR-1) is another newly described marker useful in identifying a breast primary, although in limited publications. Numerous predictive biomarkers have been evaluated, and additional studies are needed to confirm the initial findings. In genitourinary pathology, PAX8 and PAX2 have proven to be important diagnostic markers for identifying renal cell carcinoma when working on a tumor of unknown primary. ERG is a specific but not sensitive marker for prostatic adenocarcinoma. In contrast, NK3 homeobox 1 (NKX3.1) may become a highly sensitive and specific marker for prostatic adenocarcinoma if additional publications substantiate the initial reports. In limited studies, uroplakin (UP) II has proven to be a more sensitive marker than UPIII for identifying urothelial carcinoma. GATA3 and S100P are useful markers for urothelial carcinoma. A new generation Accepted for publication August 18, 2014. From the Department of Laboratory Medicine, Geisinger Medical Center, Danville, Pennsylvania. The author has no relevant financial interest in the products or companies described in this article. doi: 10.5858/arpa.2014-0294-ED Reprints: Fan Lin, MD, PhD, Department of Laboratory Medicine. Geisinger Medical Center, MC 01–31, 100 N Academy Ave, Danville, PA 17822 (e-mail: flin1@geisinger.edu).