Skip to main content
Top
Published in: Pathology & Oncology Research 4/2017

01-10-2017 | Original Article

Unusual Signal Patterns of Break-apart FISH Probes Used in the Diagnosis of Soft Tissue Sarcomas

Authors: Gergő Papp, Dóra Mihály, Zoltán Sápi

Published in: Pathology & Oncology Research | Issue 4/2017

Login to get access

Abstract

Break-apart FISH probes are the most popular and reliable type of FISH probes used to confirm certain pathological diagnoses. The interpretation is usually easy, however, in some instances it is not so unequivocal. Our aim was to reveal and elucidate the problems occurring in the process of evaluation of the break-apart probe results. Altogether 301 soft tissue sarcomas with confirmed molecular tests using break-apart probes were assessed to reveal the frequency and type of unusual signal pattern. Among 89 synovial sarcoma (SS18) 11%, 12 alveolar rhabdomyosarcoma (FOXO1) 50%, 53 myxoid liposarcoma (DDIT3) 7.5%, 6 low grade fibromyxoid sarcoma (FUS) 67%, 93 Ewing sarcoma (EWSR1) 3%, 12 clear cell sarcoma (EWSR1) 8%, 5 desmoplastic small round cell tumor (EWSR1) 0%, 9 extraskeletal myxoid chondrosarcoma (EWSR1) 0%, 2 myoepithelial carcinoma (EWSR1) 50%, 14 dermatofibrosarcoma protuberans (COL1A1) 86% and 6 nodular fasciitis (USP6) 17% atypical break-apart signals were detected. Despite the unusual signal pattern type, the fusion genes were detected using either metaphase FISH, interphase FISH with translocation/TriCheck probe or RT-PCR methods. Although the interpretation problems in the process to evaluate the break-apart probe results is well known from sporadic case reports, a systemic overview to detect their frequency has not been performed so far. In our work we highlighted the relative frequency of this problem and pinpointed those signal-patterns which, despite their unusual appearance, can still confirm the diagnosis.
Literature
1.
go back to reference Bridge JA (2014) The role of cytogenetics and molecular diagnostics in the diagnosis of soft-tissue tumors. Modern pathology: an official journal of the United States and Canadian Academy of Pathology, Inc 27(Suppl 1):S80–S97. doi:10.1038/modpathol.2013.179 CrossRef Bridge JA (2014) The role of cytogenetics and molecular diagnostics in the diagnosis of soft-tissue tumors. Modern pathology: an official journal of the United States and Canadian Academy of Pathology, Inc 27(Suppl 1):S80–S97. doi:10.​1038/​modpathol.​2013.​179 CrossRef
3.
go back to reference Fletcher CD, Organization WH, Cancer IAfRo (2013) WHO classification of tumours of soft tissue and bone. IARC press Fletcher CD, Organization WH, Cancer IAfRo (2013) WHO classification of tumours of soft tissue and bone. IARC press
6.
go back to reference Motoi T, Kumagai A, Tsuji K, Imamura T, Fukusato T (2010) Diagnostic utility of dual-color break-apart chromogenic in situ hybridization for the detection of rearranged SS18 in formalin-fixed, paraffin-embedded synovial sarcoma. Hum Pathol 41(10):1397–1404. doi:10.1016/j.humpath.2010.02.009 CrossRefPubMed Motoi T, Kumagai A, Tsuji K, Imamura T, Fukusato T (2010) Diagnostic utility of dual-color break-apart chromogenic in situ hybridization for the detection of rearranged SS18 in formalin-fixed, paraffin-embedded synovial sarcoma. Hum Pathol 41(10):1397–1404. doi:10.​1016/​j.​humpath.​2010.​02.​009 CrossRefPubMed
7.
go back to reference Argani P, Aulmann S, Karanjawala Z, Fraser RB, Ladanyi M, Rodriguez MM (2009) Melanotic Xp11 translocation renal cancers: a distinctive neoplasm with overlapping features of PEComa, carcinoma, and melanoma. Am J Surg Pathol 33(4):609–619. doi:10.1097/PAS.0b013e31818fbdff CrossRefPubMed Argani P, Aulmann S, Karanjawala Z, Fraser RB, Ladanyi M, Rodriguez MM (2009) Melanotic Xp11 translocation renal cancers: a distinctive neoplasm with overlapping features of PEComa, carcinoma, and melanoma. Am J Surg Pathol 33(4):609–619. doi:10.​1097/​PAS.​0b013e31818fbdff​ CrossRefPubMed
8.
go back to reference Amary MF, Berisha F, Bernardi Fdel C, Herbert A, James M, Reis-Filho JS, Fisher C, Nicholson AG, Tirabosco R, Diss TC, Flanagan AM (2007) Detection of SS18-SSX fusion transcripts in formalin-fixed paraffin-embedded neoplasms: analysis of conventional RT-PCR, qRT-PCR and dual color FISH as diagnostic tools for synovial sarcoma. Modern pathology: an official journal of the United States and Canadian Academy of Pathology, Inc 20(4):482–496. doi:10.1038/modpathol.3800761 CrossRef Amary MF, Berisha F, Bernardi Fdel C, Herbert A, James M, Reis-Filho JS, Fisher C, Nicholson AG, Tirabosco R, Diss TC, Flanagan AM (2007) Detection of SS18-SSX fusion transcripts in formalin-fixed paraffin-embedded neoplasms: analysis of conventional RT-PCR, qRT-PCR and dual color FISH as diagnostic tools for synovial sarcoma. Modern pathology: an official journal of the United States and Canadian Academy of Pathology, Inc 20(4):482–496. doi:10.​1038/​modpathol.​3800761 CrossRef
9.
go back to reference Matsumura T, Yamaguchi T, Seki K, Shimoda T, Wada T, Yamashita T, Hasegawa T (2008) Advantage of FISH analysis using FKHR probes for an adjunct to diagnosis of rhabdomyosarcomas. Virchows Archiv: an international journal of pathology 452(3):251–258. doi:10.1007/s00428-007-0554-9 CrossRef Matsumura T, Yamaguchi T, Seki K, Shimoda T, Wada T, Yamashita T, Hasegawa T (2008) Advantage of FISH analysis using FKHR probes for an adjunct to diagnosis of rhabdomyosarcomas. Virchows Archiv: an international journal of pathology 452(3):251–258. doi:10.​1007/​s00428-007-0554-9 CrossRef
10.
go back to reference Liu J, Guzman MA, Pezanowski D, Patel D, Hauptman J, Keisling M, Hou SJ, Papenhausen PR, Pascasio JM, Punnett HH, Halligan GE, de Chadarevian JP (2011) FOXO1-FGFR1 fusion and amplification in a solid variant of alveolar rhabdomyosarcoma. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 24(10):1327–1335. doi:10.1038/modpathol.2011.98 CrossRef Liu J, Guzman MA, Pezanowski D, Patel D, Hauptman J, Keisling M, Hou SJ, Papenhausen PR, Pascasio JM, Punnett HH, Halligan GE, de Chadarevian JP (2011) FOXO1-FGFR1 fusion and amplification in a solid variant of alveolar rhabdomyosarcoma. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 24(10):1327–1335. doi:10.​1038/​modpathol.​2011.​98 CrossRef
12.
go back to reference Smith SH, Weiss SW, Jankowski SA, Coccia MA, Meltzer PS (1992) SAS amplification in soft tissue sarcomas. Cancer Res 52(13):3746–3749PubMed Smith SH, Weiss SW, Jankowski SA, Coccia MA, Meltzer PS (1992) SAS amplification in soft tissue sarcomas. Cancer Res 52(13):3746–3749PubMed
16.
go back to reference Chien YC, Karolyi K, Kovacs I (2016) Paravertebral low-grade fibromyxoid sarcoma with supernumerary ring chromosome: case report and literature review. Ann Clin Lab Sci 46(1):90–96PubMed Chien YC, Karolyi K, Kovacs I (2016) Paravertebral low-grade fibromyxoid sarcoma with supernumerary ring chromosome: case report and literature review. Ann Clin Lab Sci 46(1):90–96PubMed
18.
go back to reference Szuhai K, IJszenga M, Tanke HJ, Taminiau AH, de Schepper A, van Duinen SG, Rosenberg C, Hogendoorn PC (2007) Detection and molecular cytogenetic characterization of a novel ring chromosome in a histological variant of Ewing sarcoma. Cancer Genet Cytogenet 172(1):12–22. doi:10.1016/j.cancergencyto.2006.07.007 CrossRefPubMed Szuhai K, IJszenga M, Tanke HJ, Taminiau AH, de Schepper A, van Duinen SG, Rosenberg C, Hogendoorn PC (2007) Detection and molecular cytogenetic characterization of a novel ring chromosome in a histological variant of Ewing sarcoma. Cancer Genet Cytogenet 172(1):12–22. doi:10.​1016/​j.​cancergencyto.​2006.​07.​007 CrossRefPubMed
19.
go back to reference Sirvent N, Maire G, Pedeutour F (2003) Genetics of dermatofibrosarcoma protuberans family of tumors: from ring chromosomes to tyrosine kinase inhibitor treatment. Genes Chromosom Cancer 37(1):1–19. doi:10.1002/gcc.10202 CrossRefPubMed Sirvent N, Maire G, Pedeutour F (2003) Genetics of dermatofibrosarcoma protuberans family of tumors: from ring chromosomes to tyrosine kinase inhibitor treatment. Genes Chromosom Cancer 37(1):1–19. doi:10.​1002/​gcc.​10202 CrossRefPubMed
20.
go back to reference Chen J, Ye X, Li Y, Wei C, Zheng Q, Zhong P, Wu S, Luo Y, Liao Z, Ye H (2014) Chromosomal translocation involving USP6 gene in nodular fasciitis. Zhonghua bing li xue za zhi = Chinese journal of pathology 43(8):533–536PubMed Chen J, Ye X, Li Y, Wei C, Zheng Q, Zhong P, Wu S, Luo Y, Liao Z, Ye H (2014) Chromosomal translocation involving USP6 gene in nodular fasciitis. Zhonghua bing li xue za zhi = Chinese journal of pathology 43(8):533–536PubMed
21.
go back to reference Geiersbach K, Rector LS, Sederberg M, Hooker A, Randall RL, Schiffman JD, South ST (2011) Unknown partner for USP6 and unusual SS18 rearrangement detected by fluorescence in situ hybridization in a solid aneurysmal bone cyst. Cancer genetics 204(4):195–202. doi:10.1016/j.cancergen.2011.01.004 CrossRefPubMed Geiersbach K, Rector LS, Sederberg M, Hooker A, Randall RL, Schiffman JD, South ST (2011) Unknown partner for USP6 and unusual SS18 rearrangement detected by fluorescence in situ hybridization in a solid aneurysmal bone cyst. Cancer genetics 204(4):195–202. doi:10.​1016/​j.​cancergen.​2011.​01.​004 CrossRefPubMed
Metadata
Title
Unusual Signal Patterns of Break-apart FISH Probes Used in the Diagnosis of Soft Tissue Sarcomas
Authors
Gergő Papp
Dóra Mihály
Zoltán Sápi
Publication date
01-10-2017
Publisher
Springer Netherlands
Published in
Pathology & Oncology Research / Issue 4/2017
Print ISSN: 1219-4956
Electronic ISSN: 1532-2807
DOI
https://doi.org/10.1007/s12253-017-0200-z

Other articles of this Issue 4/2017

Pathology & Oncology Research 4/2017 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine