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 (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.
*Department of Pathology, Faculty of Medicine in Plzen, Charles University, Prague †Bioptic Laboratory Ltd ‡Bioptic Laboratory Ltd, Molecular Pathology Laboratory, Plzen ∥The Fingerland Department of Pathology, Charles University in Prague, Faculty of Medicine and University Hospital, Hradec Kralove, Czech Republic §Department of Anatomical Pathology, University of Calgary and Foothills Medical Centre, Calgary, AB, Canada ¶Department of Pathology, Medical University of Gdansk, Gdansk, Poland.
Alena
A
Skálová
Tomas
T
Vanecek
Roderick H W
RH
Simpson
Jan
J
Laco
Hanna
H
Majewska
Martina
M
Baneckova
Petr
P
Steiner
Michal
M
Michal
D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D005260:Female; D050939:Gene Fusion; D015321:Gene Rearrangement; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D000069295:Mammary Analogue Secretory Carcinoma / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011237:Predictive Value of Tests; D011379:Prognosis; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics*; D012042:Registries; D012097:Repressor Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012468:Salivary Gland Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D055815:Young Adult; D000097764:ETS Translocation Variant 6 Protein; D020812:Receptor, trkC
D014408:Biomarkers, Tumor; D015514:Oncogene Proteins, Fusion; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D000097764:ETS Translocation Variant 6 Protein; C484319:ETV6-NTRK3 fusion protein, human; D020812:Receptor, trkC