1. ¹Medical Clinic II, University of Kiel, Kiel, Germany
2. ²Wessex Immunology Service, Molecular Pathology Unit, Southampton University Hospitals NHS Trust, Southampton, UK
3. ³Department of Pathology, CHU Henri Mondor, Créteil, France
4. ⁴Servicio de Hematologia, Hospital Universidad de Salamanca, Salamanca, Spain
5. ⁵Department of Hematology, Instituto Portugués de Oncologia, Lisboa, Portugal
6. ⁶Department of Pathology, Johann Wolfgang Goethe University Hospital, Frankfurt, Germany
7. ⁷Department of Pathology, University of Wales, Cardiff, UK
8. ⁸Institute of Pathology, Würzburg University, Würzburg, Germany
9. ⁹Laboratory d'Anatomie Pathologiques, Hospital Purpan, Toulouse, France
10. ¹⁰Servicio Central de Citometría, Universidad de Salamanca, Salamanca, Spain
11. ¹¹Institut für Hämatopathologie, University of Kiel, Kiel, Germany
12. ¹²Gerhard-Domagk Institute of Pathology, University of Münster, Münster, Germany
13. ¹³Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
14. ¹⁴Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands
15. ¹⁵Laboratory of Clinical Biology, H Hartziekenhuis, Roeselare, Belgium
16. ¹⁶Department of Pathology, UMC St Radboud, Nijmegen, The Netherlands
17. ¹⁷Department of Pathology, Medical Faculty of Porto, Porto, Portugal
18. ¹⁸Oncobiology Group, Institute for Molecular Pathology and Immunology of Porto University, Porto, Portugal
19. ¹⁹Department of Haematology, Royal Free Hospital, London, UK
20. ²⁰Department of Molecular Diagnostics, Nottingham City Hospital NHS Trust, Nottingham, UK
21. ²¹Institut für Pathologie, Charité – Universitätsmedizin Berlin, Berlin, Germany
22. ²²Laboratoire de Genetique Oncologique, Centre Henri Becquerel, Rouen, France
23. ²³Department of Haematology, Hopital Pitié-Salpétière, Paris, France
24. ²⁴Service d'Immunologie Biologique, CHU Henri Mondor, Créteil, France
25. ²⁵Laboratoire d'Hematologie, Hôpital Necker-Enfants Malades, AP-HP and Université Paris-Descartes, Paris, France
26. ²⁶Department of Pathology, Hotel-Dieu de Paris, Paris AP-HP, France

Correspondence: JJM van Dongen, Department of Immunology, Erasmus MC, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands. E-mail: j.j.m.vandongen@erasmusmc.nl

Received 31 August 2005; Revised 7 December 2005; Accepted 9 December 2005; Published online 14 December 2006.

Abstract

Polymerase chain reaction (PCR) assessment of clonal T-cell receptor (TCR) and immunoglobulin (Ig) gene rearrangements is an important diagnostic tool in mature T-cell neoplasms. However, lack of standardized primers and PCR protocols has hampered comparability of data in previous clonality studies. To obtain reference values for Ig/TCR rearrangement patterns, 19 European laboratories investigated 188 T-cell malignancies belonging to five World Health Organization-defined entities. The TCR/Ig spectrum of each sample was analyzed in duplicate in two different laboratories using the standardized BIOMED-2 PCR multiplex tubes accompanied by international pathology panel review. TCR clonality was detected in 99% (143/145) of all definite cases of T-cell prolymphocytic leukemia, T-cell large granular lymphocytic leukemia, peripheral T-cell lymphoma (unspecified) and angioimmunoblastic T-cell lymphoma (AILT), whereas nine of 43 anaplastic large cell lymphomas did not show clonal TCR rearrangements. Combined use of TCRB and TCRG genes revealed two or more clonal signals in 95% of all TCR clonal cases. Ig clonality was mostly restricted to AILT. Our study indicates that the BIOMED-2 multiplex PCR tubes provide a powerful strategy for clonality assessment in T-cell malignancies assisting the firm diagnosis of T-cell neoplasms. The detected TCR gene rearrangements can also be used as PCR targets for monitoring of minimal residual disease.