was conducted in 49 GIST cases. The concordance rate for the evaluation results at three laboratories was 90% or higher and the k value was 0.80 or more among all laboratories.Thus, essentially equal staining results were obtained in these three laboratories. It was thus confirmed that the STD method has become commonplace as the standardized method (Table 2, Figure 4). Standardization of an evaluation method for staining of Ki-67 In the assessment of a method for evaluating staining of Ki-67, the correlation between: (a) The results of a category-based evaluation giving a rough estimate of the proportion of total positive cells by visual inspection, and (b) The results of a category-based evaluation of Ki-67 LI values calculated in terms of the positive cell count by means of a counter was investigated. A very high concordance rate was obtained (94.2% concordance with a k value of 0.87; data not shown). When practical use was taken into consideration, the simpler category-based evaluation through visual inspection was, therefore, considered to be necessary. On the basis of a series of these assessment results, a simple scoring system (KI Score) comprising of four evaluation categories (stages) for anticipated use in routine diagnostic practice was devised (Table 3). Importance of KI Score in diagnosing the grade of GIST Relationships between the KI Score and the disease-free survival rate were investigated in 41 out of 52 primary GIST cases, the outcome of which could be analyzed. The median follow-up period was 36 months (18-67 months). The three-year disease-free survival rate in the group with a score of 0/1 (proportion of total positive cells <10%) and that with a score of 2/3 (proportion of total positive cells 10%) were 100% and 17%, respectively, showing a significant (P <0.0001 by log-rank test) difference. Thus, the scoring system was useful for estimating the prognosis of GIST. The relationships between other prognostic factors for GIST such as tumor size (<5 cm vs. 5 cm), mitotic counts (<5 per 50 high power field (HPF) vs. 5), and the Hornick-Fletcher risk classification (very low/low risk vs. intermediate/high risk) (2) based on these factors, and diseasefree survival rates were investigated. There were statistically significant (p = 0.0052 and p <0.0001, respectively, by log-rank test) correlations with mitotic counts and the Hornick-Fletcher risk classification. There was also a statistically significant (P = 0.0053 by Fishers exact test) relationship between mitotic counts and the KI Score. These results suggested a table corresponding to evaluation class, KI Score and risk category which is useful for evaluation of staining of Ki-67 (Table 3). Future task Improvement of the standard evaluation method established herein, comments and other technical hints (points requiring attention) can perhaps be regarded as imperative for standardizing staining of Ki-67 Since pro. viding information on the Web serves as an adjunct for rapid information dissemination, preparations are underway to provide information in this format. As regards evaluation, there has been apprehension about variations in interobserver evaluation because such evaluations are always subjective. To minimize variation, a Ki-67 staining atlas is being prepared as well. It is also essential for standardization in the assessment of tumors such as soft tissue sarcomas, brain tumors, breast cancers and endocrine tumors, for which staining of Ki-67 is recognized as being very important, that assessments initially be conducted employing the present standardization procedure for staining of Ki-67 in GIST. References 1. Hasegawa T, Matsuno Y, Shimoda T, Hirohashi S. Gastrointestinal stromal tumor: consistent CD117 immunostaining for diagnosis, and prognostic classification based on tumor size and MIB-1 grade. Hum Pathol 33: 669-676, 2002. 2. Hornick JL, Fletcher CD. The role of KIT in the management of patients with gastrointestinal stromal tumors. Hum Pathol 38: 679-687, 2007. Degree and qualification MD, PhD Japanese Pathology Board, Japanese Cytology Board Personal history 1986 MD Hokkaido University School of Medicine Sapporo, Japan 1986-1988 Clinical Resident in the Department of Orthopedic Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan 1988-1992 Pathology Resident in the Department of Pathology, University of Tokushima School of Medicine, Tokushima, Japan 1991 PhD University of Tokushima School of Medicine, Tokushima, Japan 1992-1994 Postdoctoral Research Fellow in the Department of Pathology, University of Tokushima School of Medicine, Tokushima, Japan 1994-1995 Visiting Research Fellow in the Section of Orthopedic Pathology, Department of Orthopedic Surgery, Montefiore Medical Center, University Hospital for the Albert Einstein College of Medicine, New York, U.S.A 1995-1997 Lecturer in the Department of Pathology, University of Tokushima School of Medicine, Tokushima, Japan 1997-2001 Researcher in the Pathology Division, National Cancer Center Research Institute, Tokyo, Japan 2001-2005 Head of the Pathology Division, National Cancer Center Research Institute, Tokyo, Japan 2005Professor and Director in the Department of Surgical Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan 51 | Connection 2008 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. Denver, CO NSH workshop attend New Premium Quality Concentrated Antibodies New Products Your current and future needs drive the c Targeting Colorectal Adenocarcinomas, Anti-TIMP-1 and Anti-Villin Monoclonal Mouse Anti-Human Tissue Dakos FLEX Ready-to-Use Concept Enhance performance of your laboratory by running FLEX Ready-to-Use 2008 Product Catalog Available Now! The catalog features more than 170 new products, including the A