Mammary Analogue Secretory Carcinoma of Salivary Glands: Molecular Analysis of 25 ETV6 Gene Rearranged Tumors With Lack of Detection of Classical ETV6-NTRK3 Fusion Transcript by Standard RT-PCR: Report of 4 Cases Harboring ETV6-X Gene Fusion

ETV6 gene abnormalities are well described in tumor pathology. Many fusion partners of ETV6 have been reported in a variety of epithelial and hematological malignancies. In salivary gland tumor pathology, however, the ETV6-NTRK3 translocation is specific for mammary analogue secretory carcinoma (MAS...

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Veröffentlicht in:The American journal of surgical pathology 2016-01, Vol.40 (1), p.3-13
Hauptverfasser: Skálová, Alena, Vanecek, Tomas, Simpson, Roderick H.W, Laco, Jan, Majewska, Hanna, Baneckova, Martina, Steiner, Petr, Michal, Michal
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container_title The American journal of surgical pathology
container_volume 40
creator Skálová, Alena
Vanecek, Tomas
Simpson, Roderick H.W
Laco, Jan
Majewska, Hanna
Baneckova, Martina
Steiner, Petr
Michal, Michal
description ETV6 gene abnormalities are well described in tumor pathology. Many fusion partners of ETV6 have been reported in a variety of epithelial and hematological malignancies. In salivary gland tumor pathology, however, the ETV6-NTRK3 translocation is specific for mammary analogue secretory carcinoma (MASC), and has not been documented in any other salivary tumor type. The present study comprised a clinical and molecular analysis of 25 cases morphologically and immunohistochemically typical of MASC. They all also displayed the ETV6 rearrangement as visualized by fluorescent in situ hybridization but lacked the classical ETV6-NTRK3 fusion transcript by standard reverse-transcriptase-polymerase chain reaction. In 4 cases, the classical fusion transcript was found by more sensitive, nested reverse-transcription-polymerase chain reaction. Five other cases harbored atypical fusion transcripts as detected by both standard and nested reverse-transcription-polymerase chain reaction. In addition, fluorescent in situ hybridization with an NTRK3 break-apart probe was also performed; rearrangement of NTRK3 gene was detected in 16 of 25 cases. In 3 other cases, the tissue was not analyzable, and in 2 further cases analysis could not be performed because of a lack of appropriate tissue material. Finally, in the 4 remaining cases whose profile was NTRK3 split-negative and ETV6 split-positive, unknown (non-NTRK) genes appeared to fuse with ETV6 (ETV6-X fusion). In looking for possible fusion partners, analysis of rearrangement of other kinase genes known to fuse with ETV6 was also performed, but without positive results. Although numbers were small, correlating the clinico-pathologic features of the 4 ETV6-X fusion tumors and 5 MASC cases with atypical fusion transcripts raises the possibility of that they may behave more aggressively.
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Many fusion partners of ETV6 have been reported in a variety of epithelial and hematological malignancies. In salivary gland tumor pathology, however, the ETV6-NTRK3 translocation is specific for mammary analogue secretory carcinoma (MASC), and has not been documented in any other salivary tumor type. The present study comprised a clinical and molecular analysis of 25 cases morphologically and immunohistochemically typical of MASC. They all also displayed the ETV6 rearrangement as visualized by fluorescent in situ hybridization but lacked the classical ETV6-NTRK3 fusion transcript by standard reverse-transcriptase-polymerase chain reaction. In 4 cases, the classical fusion transcript was found by more sensitive, nested reverse-transcription-polymerase chain reaction. Five other cases harbored atypical fusion transcripts as detected by both standard and nested reverse-transcription-polymerase chain reaction. In addition, fluorescent in situ hybridization with an NTRK3 break-apart probe was also performed; rearrangement of NTRK3 gene was detected in 16 of 25 cases. In 3 other cases, the tissue was not analyzable, and in 2 further cases analysis could not be performed because of a lack of appropriate tissue material. Finally, in the 4 remaining cases whose profile was NTRK3 split-negative and ETV6 split-positive, unknown (non-NTRK) genes appeared to fuse with ETV6 (ETV6-X fusion). In looking for possible fusion partners, analysis of rearrangement of other kinase genes known to fuse with ETV6 was also performed, but without positive results. 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All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3567-1cf35a79318c93d3b4cb6e188f3c5979368e1acf7b0819ac2b049398413ae96f3</citedby><cites>FETCH-LOGICAL-c3567-1cf35a79318c93d3b4cb6e188f3c5979368e1acf7b0819ac2b049398413ae96f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26492182$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Skálová, Alena</creatorcontrib><creatorcontrib>Vanecek, Tomas</creatorcontrib><creatorcontrib>Simpson, Roderick H.W</creatorcontrib><creatorcontrib>Laco, Jan</creatorcontrib><creatorcontrib>Majewska, Hanna</creatorcontrib><creatorcontrib>Baneckova, Martina</creatorcontrib><creatorcontrib>Steiner, Petr</creatorcontrib><creatorcontrib>Michal, Michal</creatorcontrib><title>Mammary Analogue Secretory Carcinoma of Salivary Glands: Molecular Analysis of 25 ETV6 Gene Rearranged Tumors With Lack of Detection of Classical ETV6-NTRK3 Fusion Transcript by Standard RT-PCR: Report of 4 Cases Harboring ETV6-X Gene Fusion</title><title>The American journal of surgical pathology</title><addtitle>Am J Surg Pathol</addtitle><description>ETV6 gene abnormalities are well described in tumor pathology. 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In addition, fluorescent in situ hybridization with an NTRK3 break-apart probe was also performed; rearrangement of NTRK3 gene was detected in 16 of 25 cases. In 3 other cases, the tissue was not analyzable, and in 2 further cases analysis could not be performed because of a lack of appropriate tissue material. Finally, in the 4 remaining cases whose profile was NTRK3 split-negative and ETV6 split-positive, unknown (non-NTRK) genes appeared to fuse with ETV6 (ETV6-X fusion). In looking for possible fusion partners, analysis of rearrangement of other kinase genes known to fuse with ETV6 was also performed, but without positive results. 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Many fusion partners of ETV6 have been reported in a variety of epithelial and hematological malignancies. In salivary gland tumor pathology, however, the ETV6-NTRK3 translocation is specific for mammary analogue secretory carcinoma (MASC), and has not been documented in any other salivary tumor type. The present study comprised a clinical and molecular analysis of 25 cases morphologically and immunohistochemically typical of MASC. They all also displayed the ETV6 rearrangement as visualized by fluorescent in situ hybridization but lacked the classical ETV6-NTRK3 fusion transcript by standard reverse-transcriptase-polymerase chain reaction. In 4 cases, the classical fusion transcript was found by more sensitive, nested reverse-transcription-polymerase chain reaction. Five other cases harbored atypical fusion transcripts as detected by both standard and nested reverse-transcription-polymerase chain reaction. In addition, fluorescent in situ hybridization with an NTRK3 break-apart probe was also performed; rearrangement of NTRK3 gene was detected in 16 of 25 cases. In 3 other cases, the tissue was not analyzable, and in 2 further cases analysis could not be performed because of a lack of appropriate tissue material. Finally, in the 4 remaining cases whose profile was NTRK3 split-negative and ETV6 split-positive, unknown (non-NTRK) genes appeared to fuse with ETV6 (ETV6-X fusion). In looking for possible fusion partners, analysis of rearrangement of other kinase genes known to fuse with ETV6 was also performed, but without positive results. Although numbers were small, correlating the clinico-pathologic features of the 4 ETV6-X fusion tumors and 5 MASC cases with atypical fusion transcripts raises the possibility of that they may behave more aggressively.</abstract><cop>United States</cop><pub>Copyright Wolters Kluwer Health, Inc. All rights reserved</pub><pmid>26492182</pmid><doi>10.1097/PAS.0000000000000537</doi><tpages>11</tpages></addata></record>
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subjects Adolescent
Adult
Aged
Biomarkers, Tumor - genetics
ETS Translocation Variant 6 Protein
Female
Gene Fusion
Gene Rearrangement
Genetic Predisposition to Disease
Humans
Immunohistochemistry
In Situ Hybridization, Fluorescence
Male
Mammary Analogue Secretory Carcinoma - chemistry
Mammary Analogue Secretory Carcinoma - genetics
Mammary Analogue Secretory Carcinoma - pathology
Mammary Analogue Secretory Carcinoma - therapy
Middle Aged
Molecular Diagnostic Techniques
Oncogene Proteins, Fusion - genetics
Predictive Value of Tests
Prognosis
Proto-Oncogene Proteins c-ets - genetics
Registries
Repressor Proteins - genetics
Reverse Transcriptase Polymerase Chain Reaction
Salivary Gland Neoplasms - chemistry
Salivary Gland Neoplasms - genetics
Salivary Gland Neoplasms - pathology
Salivary Gland Neoplasms - therapy
Young Adult
title Mammary Analogue Secretory Carcinoma of Salivary Glands: Molecular Analysis of 25 ETV6 Gene Rearranged Tumors With Lack of Detection of Classical ETV6-NTRK3 Fusion Transcript by Standard RT-PCR: Report of 4 Cases Harboring ETV6-X Gene Fusion
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