Editorial Immunohistochemistry (IHC) Standardization Around the World George L. Kumar, PhD Managing Editor Welcome to another informative issue of Connection, our special issue devoted to IHC Standardization Around the World This issue . includes opinions, articles and questions and answers from IHC experts in Australia, Brazil, Canada, China, Denmark, India, Japan, the United Kingdom and the United States. Thanks to the advent of modern communication technology, this entire report was compiled remotely by electronic communications and telephone conversations with the experts. In brief, this issue highlights the challenges that lie ahead in standardizing IHC around the world. For instance, the technical problems that developed countries (Australia, Canada, Denmark, Japan, the United Kingdom and the United States) and developing countries (China, Brazil and India) are facing are nearly the same. Most laboratories around the world have no control over the pre-analytical factors, i.e. mainly tissue handling following surgery and prior to submission to the laboratory. In a similar manner, one of the analytical variables, i.e. duration of tissue exposure to the fixative, seems to vary a lot between laboratories in all these countries. However, the existing problems in developing countries are different from those in developed countries in terms of basic education in laboratory practice and infrastructure as well as in terms of quantity of samples received by pathologists. In India, the allopathic doctor-population ratio is about 1:1700 (1) and the number of patients attended by a physician in a rural area can be as high as 300 per day (2). This results in enormous workloads to all medical professionals ­ including pathologists ­ leading to quality control issues associated with patient samples. In Brazil, the doctor-population ratio is higher, 1:900, but the problem here stems from the lack of adequate laboratory training and other associated costs. There are other issues too: The lack of funds to buy the most basic equipment (think of Africa), expenses associated with visiting state-of-the-art diagnostic centers in the developed world and last, but not least, no organizational structure provided by orginazations such as e.g. USCAP, UK NEQAS or NordiQC that can promote standardization. All this leads to one rhetorical question: Can standardization of IHC testing be achieved? The answer is an unqualified Yes But unless . every country works toward developing its own national standardization organization and take part in an international meeting represented by the heads of such organizations (such as the Intergovernmental Panel on Climate Change, or IPCC meetings), standardization around the world is not possible. The challenge for all of us is to act in a serious, yet timely fashion given the liabilities that exist for the patient. While uncertainties remain, we can at least begin to address the factors that contribute to a consensus in this regard. I welcome debate and suggestions. 1. Emerging India/Foreigners taking advantage of cheap, high-quality medical care. The Yomiuri Shimbun. Feb. 4, 2007 http://www.yomiuri.co.jp/dy/world/20070204TDY01003.htm. . 2. Number of Inhabitants per Doctor. EuroRSCG Amsterdam, Netherlands. http://adsoftheworld.com/media/print/doctors_of_the_world_netherlands_perspective?size=_original. Connection 2008 | 2 April 2008, VOL 11 Connection IHC STANDARDIZATION AROUND THE WORLD In this issue Q&A with Patho Contents APRIL 2008, VOL 11 2 3 4 Editorial George L. Kumar, PhD Featured Laboratory The Osamura Editorial Immunohistochemistry (IHC) Standardization Around the World George L. Kumar, PhD Managing Featured Laboratory The Osamura Laboratory Laboratory headed by Prof. Robert Yoshiyuki Osamura, MD, Q&A Ask the Experts: On Immunohistochemistry (IHC) Standardization Professor Leong is Medical Di time interval between removal of tissue and immersion in fixative, the temperature of tissue storage Connection: How would you like to standardize IHC in Australia? As discussed above, standardization Connection: Antigen retrieval is essential in immunohistochemistry (IHC) in order to restore epitope Connection: Is a universal image analysis system feasible? No, not until we standardize the all impo Q&A Fernando Soares, MD, PhD University of São Paulo, São Paulo, Brazil Dr. Fernando Soares is F Connection: In your opinion, what is the biggest hurdle for standardization? Probably education in l There are no standards in Latin America. We always follow the manufacturers protocol during our firs Q&A Bryan R. Hewlett, ART, MLT Consultant Technologist to the Anatomic Pathology EQA program of There is no standardization of AR steps circumstances, it would be impossible toand, undera the pre Connection: How would you rate European (UK NEQAS, NordiQC) and US IHC standards to Canadian IHC sta Q&A Prof. Chen Jie Prof. Cui Quancai Peking Union Mediacl College Hospital, Beijing, China Prof. Connection: According to Goldstein et al. Appl Immunohistochem Mol Morphol 2007;15:124­133 Immunohis Connection: Is it true that a particular histology feature may be better demonstrated by other fixat Connection: What constitutes standardization of image analysis as applied to immunohistochemistry (I Q&A Dr. Tanuja Manjanath Shet Dr. Vani Parmar Tata Memorial Hospital, Mumbai, India Tanuja Manj ... the biggest hurdle in India is suboptimal fixation and processing of tissues. Though I agree th Connection: Is it true that a particular histology feature may be better demonstrated by other fixat Connection: Can you comment on the internal and external quality control (EQC) procedures followed i Q&A Prof. Robert Yoshiyuki Osamura Department of Pathology, Tokai University School of Medicine Connection: In your opinion, what is the biggest hurdle for standardization? The biggest hurdle for the standardization of image ... appropriate for pre-screeninganalysis is of the staining quality. Connection: Why is standardization of image analysis in diagnostic pathology important? Because the Q&A James F. Happel, DLM (ASCP), HTL Technical Director of Surgical Pathology, Research and Deve Connection: United Kingdom National External Quality Assessment Service (UK NEQAS) helps to ensure t Connection: The American Society of Clinical Oncology (ASCO) and the College of American Pathologist would recommend that standardization Ibegin with identifying a reliable and trustworthy source ... Interview Immunohistochemistry for Oestrogen and Progesterone Receptors Dr. Andrew Lee Consultant H Connection: What is the difference between the H score and the Allred score? Which is better? What d Connection: Can you comment on the burden in the laboratory, if one changes from a current ER/PR ass Opinion & Interview IHC Standardization: A Dako Perspective Dr. Ole Rasmussen R&D Director, Connection: Dako has developed Readyto-Use Antibodies for in vitro diagnostic applications. How is t Articles UK NEQAS-ICC & ISH: Historical perspective, current role, future directions Andy Dodso UK NEQAS-ICC in the 1990s In his first year as Scheme Organiser, Keith oversaw the transition to sub The application could be argued to represent a field change in terms of the rigour with which the an Assessment teams consist of four assessors, who view slides around a multi-headed microscope and sco The archive which UK NEQAS holds, both in terms of stained slides and methodological data, must sure For Immunocytochemistry and FISH RESULT: RUN 80L SLIDE: NEQAS Laboratory No: XXX Mr. A. Scientist De Figure 6. Feedback on results has always been given high priority, and for many years this has been a b c d Figure 7. The antigen chosen by Gerry Reynolds for his very first assessment run was kap Bibliography Selected UK NEQAS-ICC & ISH papers. Ibrahim M, Dodson AR, Barnett S, Fish D, Jasani Articles Nordic Immunohistochemical Quality Control (NordiQC) An Organization for External Quality A parameters (i.e. results interpretation and reporting) (4, 5). In an EQA setting, by circulating ser CD79a (Fig. 2) Among 112 laboratories submitting stains in the latest run, most used mAb clone JCB11 References 1. Rhodes A, Jasani B, Barnes DM, Bobrow LG, Miller KD. Reliability of immuno-histochemic Fig. 2. CD79a A. Optimal CD79a staining of the tonsil using the monoclonal antibody (mAb) clone JCB Standardization of Ki-67 Immunohistochemical Staining for Diagnosing Grade of Gastrointestinal Strom was conducted in 49 GIST cases. The concordance rate for the evaluation results at three laboratorie CB pH6 a b c d TE pH9 e f g h Autoclave 121° C/10 min Water bath 95° C/40 min Microwave 50 Table 1. Correlation between NCC and STD methods R2=0.9483 Categories of proportion NCC Method 3 Opinions Importance of Standardization for Predictive Prognosis David J. Dabbs, MD Chief of Pathol is documented and serves as a surrogate marker for the initial exposure to formalin. Since the first Opinions The New Era for ER and PRIts time to Standardize! Dr. Ian Ellis, B.Med.Sci. BM, MS, FRCpa et al 2001). The main reason for false-negative results is due to inefficient heat-induced epitope ( Standardization of HER2 TestingInconsistency Raises Questions Opinions Sunil S. Badve, MD, FRCPath rence seen in these trials is in the order of 50%. This is the major reason for all the excitement a which now requires expression of HER2 by at least 30% of tumor cells (instead of 10%). It has also r IHC CONSENSUS MEETING, JANUARY 27 2008, SANTA BARBARA, CA, USA , IHC CONSENSUS MEETING, JANUARY 27, Richard Cartun, PhD, Sunil Badve, MD Jon Askaa, PhD Søren Nielsen, HT, CT, Mogens Vyberg, MD Elizab Dako Abstracts Abstracts presented at the 30th Annual San Antonio Breast Cancer Symposium December Dako Abstracts Amplification of ESR1 may predict resistance to adjuvant tamoxifen in postmenopausal Dako Abstracts Abstracts presented at the United States and Canadian Academy of Pathology (USCAP) A Dako Abstracts Metastatic Pancreatic Endocrine Tumors in the Liver Express KOC Briones AJ, Bourne P Dako Abstracts Merkel Cell Carcinomas Express K Homology Domain Containing Protein Overexpressed in Dako Abstracts Immunohistochemical Analysis of KOC/IMP3 in Malignant Pleural Mesothelioma Xu H, Sim Dako Abstracts KOC, TTF-1 and CDX2 Discriminate Small-Cell Carcinoma from Carcinoid and Pancreatic Dako Publications Publications Co-authored by Dako: In Press Li L, Xu H, Spaulding B, Cheng L, Si Dako Meetings 2007 - National Society for Histotechnology Meeting. 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