title: Mammary analogue secretory carcinoma of salivary glands with high-grade transformation: report of 3 cases with the ETV6-NTRK3 gene fusion and analysis of TP53, β-catenin, EGFR, and CCND1 genes.
abstract: Mammary analogue secretory carcinoma of salivary gland origin (MASC) is a recently described tumor resembling secretory carcinoma of the breast characterized by strong S-100 protein, mammaglobin, and vimentin immunoexpression and which harbors a t(12;15) (p13;q25) translocation resulting in ETV6-NTRK3 fusion product. Histologically, conventional MASC displays bland histomorphology and a lobulated growth pattern and is often composed of microcystic, tubular, and solid structures with abundant eosinophilic homogenous or bubbly secretions. Colloid-like secretory material stains positively for periodic acid-Schiff with and without diastase as well as for Alcian Blue. We present for the first time, 3 patients with MASC of the parotid gland in which high-grade (HG) transformation developed in each case characterized by an accelerated clinical course and poor outcome. The HG component revealed strong membrane staining for EGFR and β-catenin, cytoplasmic/nuclear staining for S-100 protein, and nuclear staining for cyclin-D1, whereas HER-2/neu was absent. Analysis for the presence of the ETV6-NTRK3 fusion transcript revealed positivity in both HG and low-grade component of MASC in 2 of the 3 studied cases. The tumor in case 2 was negative in both its elements for the t(12;15) translocation, but ETV6 gene rearrangement was detected in both components in all 3 cases. Analysis of TP53 and CTNNB1 gene mutations in the HG component of MASCs as well as detection of copy number aberration of EGFR and CCND1 gene did not harbor any abnormalities. All 3 patients with HG-transformed MASC died of disseminated disease within 2 to 6 years after diagnosis. Recognizing HG-transformed MASC and testing for ETV6 rearrangement may be of potential value in patient treatment, because the presence of the ETV6-NTRK3 translocation may represent a therapeutic target in MASC.
authors.affiliation: *Department of Pathology, Faculty of Medicine in Plzen, Charles University in Prague †Bioptic Laboratory Ltd ‡Bioptic Laboratory Ltd, Molecular Pathology Laboratory #Department of Maxillofacial Surgery, Faculty of Medicine, Clinic of Dentistry, Plzen ∥The Fingerland Department of Pathology, Faculty of Medicine and University Hospital, Charles University in Prague, Hradec Kralove, Czech Republic §Department of Pathology, Medical University of Gdansk, Poland ¶Department of Anatomical Pathology, University of Calgary and Foothills Medical Centre, Calgary, AB, Canada.
authors.forename: Alena
authors.initials: A
authors.lastname: Skálová
authors.forename: Tomas
authors.initials: T
authors.lastname: Vanecek
authors.forename: Hanna
authors.initials: H
authors.lastname: Majewska
authors.forename: Jan
authors.initials: J
authors.lastname: Laco
authors.forename: Petr
authors.initials: P
authors.lastname: Grossmann
authors.forename: Roderick H W
authors.initials: RH
authors.lastname: Simpson
authors.forename: Lukas
authors.initials: L
authors.lastname: Hauer
authors.forename: Pavel
authors.initials: P
authors.lastname: Andrle
authors.forename: Lubor
authors.initials: L
authors.lastname: Hosticka
authors.forename: Jindrich
authors.initials: J
authors.lastname: Branžovský
authors.forename: Michal
authors.initials: M
authors.lastname: Michal
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D001706:Biopsy; D002277:Carcinoma / Q000737:chemistry / Q000235:genetics* / Q000556:secondary / Q000628:therapy; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology; D019938:Cyclin D1 / Q000032:analysis / Q000235:genetics*; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000032:analysis / Q000235:genetics*; D017809:Fatal Outcome; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D010307:Parotid Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D011379:Prognosis; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D051176:beta Catenin / Q000032:analysis / Q000235:genetics*; D020812:Receptor, trkC; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D014408:Biomarkers, Tumor; D019938:Cyclin D1; D066246:ErbB Receptors; D015514:Oncogene Proteins, Fusion; D016159:Tumor Suppressor Protein p53; D051176:beta Catenin; C530104:CCND1 protein, human; C495270:CTNNB1 protein, human; C484319:ETV6-NTRK3 fusion protein, human; D020812:Receptor, trkC; D000097764:ETS Translocation Variant 6 Protein; C495901:TP53 protein, human; C512478:EGFR protein, human