Alexander Fichtner1, Annika Richter1, Simon Filmar1, Nadine T Gaisa2, Stefan Schweyer3, Henning Reis4, Daniel Nettersheim5, Christoph Oing6, Fabian A Gayer7, Andreas Leha8, Stefan Küffer1, Philipp Ströbel1, Silke Kaulfuß9, Felix Bremmer1. 1. Institute of Pathology, University Medical Centre, Göttingen, Germany. 2. Institute of Pathology, RWTH Aachen University, Aachen, Germany. 3. Gemeinschaftspraxis Pathologie, Starnberg, Germany. 4. Institute of Pathology, West German Cancer Centre, University of Duisburg-Essen, University Hospital Essen, Essen, Germany. 5. Department of Urology, Urological Research Laboratory, Translational UroOncology, University Hospital Düsseldorf, Düsseldorf, Germany. 6. Department of Oncology, Haematology and Bone Marrow Transplantation with Division of Pneumology, Mildred Scheel Cancer Career Centre HaTriCS4, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany. 7. Department of Urology, University Medical Centre, Göttingen, Germany. 8. Institute of Medical Statistics, University Medical Centre, Göttingen, Germany. 9. Institute of Human Genetics, University Medical Centre, Göttingen, Germany.
Abstract
AIMS: Malignant germ cell tumours (GCTs) of the testis are rare neoplasms, but the most common solid malignancies in young men. World Health Organization guidelines divide GCTs into five types, for which numerous immunohistochemical markers allow exact histological subtyping in the majority of cases. In contrast, a germ cell origin is often hard to prove in metastatic GCTs that have developed so-called somatic malignant transformation. A high percentage, up to 89%, of GCTs are characterised by the appearance of isochromosome 12p [i(12p)]. Fluorescence in-situ hybridisation has been the most common diagnostic method for the detection of i(12p) so far, but has the disadvantages of being time-consuming, demanding, and not being a stand-alone method. The aim of the present study was to establish a quantitative real-time polymerase chain reaction assay as an independent method for detecting i(12p) and regional amplifications of the short arm of chromosome 12 by using DNA extracted from formalin-fixed paraffin-embedded tissue. METHODS AND RESULTS: A cut-off value to distinguish between the presence and absence of i(12p) was established in a control set consisting of 36 tumour-free samples. In a training set of 149 GCT samples, i(12p) was detectable in 133 tumours (89%), but not in 16 tumours (11%). In a test set containing 27 primary and metastatic GCTs, all 16 tumours with metastatic spread and/or somatic malignant transformation were successfully identified by the detection of i(12p). CONCLUSION: In summary, the qPCR assay presented here can help to identify, further characterise and assign a large proportion of histologically inconclusive malignancies to a GCT origin.
AIMS: Malignant germ cell tumours (GCTs) of the testis are rare neoplasms, but the most common solid malignancies in young men. World Health Organization guidelines divide GCTs into five types, for which numerous immunohistochemical markers allow exact histological subtyping in the majority of cases. In contrast, a germ cell origin is often hard to prove in metastatic GCTs that have developed so-called somatic malignant transformation. A high percentage, up to 89%, of GCTs are characterised by the appearance of isochromosome 12p [i(12p)]. Fluorescence in-situ hybridisation has been the most common diagnostic method for the detection of i(12p) so far, but has the disadvantages of being time-consuming, demanding, and not being a stand-alone method. The aim of the present study was to establish a quantitative real-time polymerase chain reaction assay as an independent method for detecting i(12p) and regional amplifications of the short arm of chromosome 12 by using DNA extracted from formalin-fixed paraffin-embedded tissue. METHODS AND RESULTS: A cut-off value to distinguish between the presence and absence of i(12p) was established in a control set consisting of 36 tumour-free samples. In a training set of 149 GCT samples, i(12p) was detectable in 133 tumours (89%), but not in 16 tumours (11%). In a test set containing 27 primary and metastatic GCTs, all 16 tumours with metastatic spread and/or somatic malignant transformation were successfully identified by the detection of i(12p). CONCLUSION: In summary, the qPCR assay presented here can help to identify, further characterise and assign a large proportion of histologically inconclusive malignancies to a GCT origin.
Authors: Annika Richter; Alexander Fichtner; Jasmin Joost; Hanibal Bohnenberger; Philipp Brockmeyer; Philipp Kauffmann; Henning Schliephake; Alexander Hammerstein-Equord; Stefan Kueffer; Henning Urlaub; Thomas Oellerich; Philipp Ströbel; Felix Bremmer Journal: J Pathol Clin Res Date: 2021-10-14
Authors: Ciara Conduit; Wei Hong; Felicity Martin; Benjamin Thomas; Nathan Lawrentschuk; Jeremy Goad; Peter Grimison; Nariman Ahmadi; Ben Tran; Jeremy Lewin Journal: Front Oncol Date: 2022-08-17 Impact factor: 5.738