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Hans Kreipe

The need to standardize marker analysis in cancer – experiences with lymphomas and other neoplasms

Handout

For classification of tumours and prediction of potential benefit from targeted therapies pathologists apply immunohistochemistry and molecular methods. In order to meet the increasing demand for quality assured predictive pathology we founded a quality assurance system for German pathologists in 2002. Since then annual or bi-annual round robin tests with up to 250 participants have been conducted to the following types of analysis:

Tumour Marker Methods
Bronchogenic carcinoma Mutation of Epidermal Growth Factor Receptor PCR, Sequencing
Bronchogenic carcinoma EML 4 ALK translocation Immunohistochemistry,
In-situ-Hybridisation
Gastrointestinal stroma tumor PDGFR-A, c-kit PCR, Sequencing
Colon cancer K-ras PCR, Sequencing
Colon cancer Mikrosatellite instability PCR,
Immunhistochemistry
Gastric cancer HER2 Immunhistochemistry,
In-situ-Hybridisation
Lymphoma Immunophenotyping Immunhistochemistry
Lymphoma Receptor rearrangement for anlysis of clonality PCR, electophoresis
Malignant melanoma B-raf PCR, Sequencing
Breast cancer Estrogen receptor Immunohistochemistry
Breast cancer Progesterone receptor Immunohistochemistry
Breast cancer HER2 Immunohistochemistry,
In-situ-Hybridisation
Breast cancer, lymphoma, neuroendocrine tumors Ki-67 Immunohistochemistry

The quality assurance trials are based on sections from human samples, either as tissue micro- arrays or as unstained sections for molecular studies. Only material which was identically tested by three independent reference institutes before is entered into the trials.

With regard to lymphoma, immunohenotyping, rearrangement analysis and Ki-67 have been standardized by round robin tests. These results will be presented.

In addition, a web based system to benchmark individual HER2 results with the majority of laboratories has been introduced (Choritz et al. Quality assessment of HER2 testing by monitoring of positivity rates. Virchows Arch. 2011;459:283-9; http://webhost1.mh-hannover.de/pat/Anmeldung1.htm). Up to now 41,000 HER2 assessments have been entered into the system. The average positivity rate is far lower than could have been expected from the literature and ranges between 15% and 16%. Institutes are informed by a traffic light indicator whether their positivity rates in relation to the number of assessments lies within or outside of 95% and 99.5% confidence intervals.

Since the introduction of round robin tests and other measurements to assure standardization of immunohistochemistry and in-situ hybridization an improvement of concordance between local and central testing of HER2 could be demonstrated. This became evident from neoadjuvant treatment studies. Complete pathological response based on local HER2 testing increased from 20% (2006) to over 40% (2011), thus being close to the results of the central pathology.

CV

Hans Kreipe, Prof. Dr. med., Date of Birth: August 24, 1956

Department: Institute of Pathology, Medizinische Hochschule Hannover Carl-Neuberg-Str. 1, D-30625 Hannover Phone: 0511/532-6067, Fax: 0511/532-6068 e-mail: Kreipe.Hans@MH-Hannover.De http://www.mh-hannover.de/pathologie.html

Education:

1976-82 Study of Medicine, University of Kiel

Academic appointments:

1984-91 Resident, Institute of Pathology Kiel (Prof. Dr. Karl Lennert)

1985 Doctoral thesis (Prof. Parwaresch, Kiel)

1991 Habilitation

1991-93 Senior Registrar Institute of Pathology, Kiel (Prof. Dr. M. Dietel)

1993-98 Professor of Pathology and deputy director of the Institute of Pathology University of Würzburg (Prof. Dr. K. Müller–Hermelink)

1998- Full Professor, Director Institute of Pathology, Hannover Medical School, Hannover

Other professional activities:

2001-2010 Board member, German Society of Pathology

2002- Board member, European Bone Marrow Working Group

2007-2010 Chairperson European Bone Marrow Working Group

2007-2010 Board member, European Association of Hematopathology

2008 Member of the German Academy of Science (Leopoldina) 2008 Congress-President German Society of Senology     2010 Congress-President German Society of Pathology     2010- Board member European Society of Pathology

Reviewer for DFG, DAAD, Deutsche Krebshilfe, Sander-Stiftung, Leukemia&Lymphoma Research Fund, U.K., and various international foundations and universities

Editorial Board of Virchows Archive, Annals of Hematology

Awards:

2008 Jeremy Jazz Prize for Research Excellence in Pathology (shared)

Professional Societies:

American Association for Cancer Research, European Society of Pathology, European Association of Hematopathology, European Bone Marrow Working Group, German Society of Pathology, German Society of Senology, International Academy of Pathology

Major Research Interests:

  1. Breast Cancer
  2. Hematopathology
  3. Molecular Pathology

Selected Publications on Standardization of Immunohistochemistry and Molecular Pathology:

  1. Choritz H, Büsche G, Kreipe H; Study Group HER2 Monitor. Quality assessment of HER2 testing by monitoring of positivity rates. Virchows Arch. 2011 Sep;459(3):283-9.
  2. van Krieken JH, Normanno N, Blackhall F, Boone E, Botti G, Carneiro F, Celik I, Ciardiello F, Cree IA, Deans ZC, Edsjö A, Groenen PJ, Kamarainen O, Kreipe HH, Ligtenberg MJ, Marchetti A, Murray S, Opdam FJ, Patterson SD, Patton S, Pinto C, Rouleau E, Schuuring E, Sterck S, Taron M, Tejpar S, Timens W, Thunnissen E, van de Ven PM, Siebers AG, Dequeker E.Guideline on the requirements of external quality assessment programs in molecular pathology. Virchows Arch. 2013 Jan;462(1):27-37. doi: 10.1007/s00428-012-1354-4. Epub 2012 Dec 19
  3. Denkert C, Kronenwett R, Schlake W, Bohmann K, Penzel R, Weber KE, Höfler H, Lehmann U, Schirmacher P, Specht K, Rudas M, Kreipe HH, Schraml P, Schlake G, Bago-Horvath Z, Ticket F, Varga Z, Moch H, Schmidt M, Prinzler J, Kerjaschki D, Sinn BV, Müller BM, Filipits M, Petry C, Dietel M. Decentral gene expression analysis for ER+/Her2- breast cancer: results of a proficiency testing program for the EndoPredict assay. Virchows Arch. 2012 Mar;460(3):251-9. doi: 10.1007/s00428-012-1204-4.
  4. Kreipe HH.[Receptor detection in breast cancer. A decade of quality assurance trials in German-speaking pathology].Pathologe. 2011 Sep;32(5):357-9. doi: 10.1007/s00292-011-1522-3.
  5. Valent P, Orazi A, Büsche G, Schmitt-Gräff A, George TI, Sotlar K, Streubel B, Beham-Schmid C, Cerny-Reiterer S, Krieger O, van de Loosdrecht A, Kern W, Ogata K, Wimazal F, Várkonyi J, Sperr WR, Werner M, Kreipe H, Horny HP.Standards and impact of hematopathology in myelodysplastic syndromes (MDS).Oncotarget. 2010 Nov;1(7):483-96. Review.
  6. Penzel R, Sers C, Chen Y, Lehmann-Mühlenhoff U, Merkelbach-Bruse S, Jung A, Kirchner T, Büttner R, Kreipe HH, Petersen I, Dietel M, Schirmacher P.EGFR mutation detection in NSCLC--assessment of diagnostic application and recommendations of the German Panel for Mutation Testing in NSCLC. Virchows Arch. 2011 Jan;458(1):95-8. doi: 10.1007/s00428-010-1000-y. Epub 2010 Nov 6
  7. Rüschoff J, Dietel M, Baretton G, Arbogast S, Walch A, Monges G, Chenard MP, Penault-Llorca F, Nagelmeier I, Schlake W, Höfler H, Kreipe HH.HER2 diagnostics in gastric cancer-guideline validation and development of standardized immunohistochemical testing. Virchows Arch. 2010 Sep;457(3):299-307. doi: 10.1007/s00428-010-0952-2..
  8. von Wasielewski R, Krusche CA, Rüschoff J, Fisseler-Eckhoff A, Kreipe H. Implementation of External Quality Assurance Trials for Immunohistochemically Determined Breast Cancer Biomarkers in Germany. Breast Care (Basel). 2008;3(2):128-133. Epub 2008 Apr 15
  9. Wasielewski R, Hasselmann S, Rüschoff J, Fisseler-Eckhoff A, Kreipe H. Proficiency testing of immunohistochemical biomarker assays in breast cancer. Virchows Arch. 2008 Dec;453(6):537-43.
  10. Krusche CA, von Wasielewski R, Rüschoff J, Fisseler-Eckhoff A, Kreipe HH. [Interlaboratory trials for quality assurance of breast cancer biomarkers in Germany.] Pathologe. 2008 Jul;29(4):315-20.
  11. Kreipe HH, von Wasielewski R. Beyond typing and grading: target analysis in individualized therapy as a new challenge for tumour pathology. Recent Results Cancer Res. 2007;176:3-6.
  12. Dietel M, Ellis I, Höfler H, Kreipe H, Moch H, Dankof A, Kölble K, Kristiansen G: Comparison of automated silver enhanced in-situ hybridisation (SISH) and fluorescence-ISH (FISH) for the validation of HER2 gene status in breast carcinoma according to the guidelines of the American Society of Clinical Oncology and the College of American Pathologists. Virchow's Arch 2007; 451(1): 19-25
  13. Mengel M, Hebel K, Kreipe H, von Wasielewski R.Standardized on-slide control for quality assurance in the immunohistochemical assessment of therapeutic target molecules in breast cancer. Breast J. 2005;11:34-40.
  14. Mengel M, Kreipe H, von Wasielewski R. Rapid and large-scale transition of new tumor biomarkers to clinical biopsy material by innovative tissue microarray systems. Appl Immunohistochem Mol Morphol. 2003 Sep;11(3):261-8.
  15. Rudiger T, Hofler H, Kreipe HH, Nizze H, Pfeifer U, Stein H, Dallenbach E, Fischer HP, Mengel M, Von Wasielewski R, Muller-Hermelink K; German Society for Pathology; Professional Association of German Pathologists. [Interlaboratory trial 2000 " Immunohistochemistry" of the German Society for Pathology and the Professional Association of German Pathologists]Pathologe. 2003 Feb;24(1):70-8
  16. von Wasielewski R, Mengel M, Wiese B, Rudiger T, Muller-Hermelink HK, Kreipe H: Tissue array technology for testing interlaboratory and interobserver reproducibility of immunohistochemical estrogen receptor analysis in a large multicenter trial. Am J Clin Pathol 2002, 118:675-682
  17. Mengel M, von Wasielewski  R, Wiese B, Rüdiger T, Müller-Hermelink HK, Kreipe H. Interlaboratory and interobserver reproducibility of immunohistochemical assessment of the Ki67-labelling index in a large multi-centre trial. J Pathol. 2002 Nov;198(3):292-9.
  18. Rudiger T, Hofler H, Kreipe HH, Nizze H, Pfeifer U, Stein H, Dallenbach FE, Fischer HP, Mengel M, von Wasielewski R,  Muller-Hermelink HK. Quality assurance in immunohistochemistry: results of an interlaboratory trial involving 172 pathologists. Am J Surg Pathol. 2002 Jul;26(7):873-82.
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