Mammary analogue secretory carcinoma (MASC) of the salivary gland was first described by Skálová in 2010. A chromosome translocation was found to be identical to the t(12;15) (p13;q25)found in secretory carcinoma of the breast. This fusion is between the gene.
The fusion gene product contains the N-terminus of the transcription faction TEL that is responsible for dimerization/ polymerization ETV6. The C-terminus of the protein product of the gene fusion contains the C-terminus of the receptor tyrosine kinase Tropomyosin receptor kinase C. It should be noted that the fusion protein lacks regulation by growth factors. Since it's discovery, much of the literature concerning MASC has addressed the challenge of differentiating it from similar appear cancers such as acinic cell carcinoma (AciCC), low-grade cribriform cystadenocarcinoma (LGCCC), and adenocarcinoma not otherwise specified (AcNOS). Means of identifying and differentiating MASC rely on histology, protein markers, and genetic markers.
Protein Expression Presence of
S100, a family of calcium binding proteins. Many of the antibodies used in MASC studies are specific to the S100B isoform.
Mammaglobin, a breast cancer marker
cytokeratin CK7, Keratin 7, an intermediate filament found in epithelial cells.
GATA3, a transcription factor that is a breast cancer biomarker.
SOX10, a transcription factor important in neural crest origin cells and in development of the peripheral nervous system.
STAT5A, a transcription factor
Absence of
TP63, a transcription factor in the same family as p53
DOG1 Discovered On Gastrointestinal Stromal Tumors Protein) otherwise known as Anoctamin-1, a voltage sensitive calcium activated chloride channel.
lobulated growth pattern
microcystic Cyst and glandular spaces
eosinophilic secretions, i.e. stains strongly for eosin Y
positive for periodic acid-Schiff stain, often after diastase
Vesicular oval nuclei with a single small but prominent nucleolus
absence of basophilic Haematoxylin or Zymogengranules found in AciCC
Chromosome break at the ETV6 loci using Fluorescence in situ hybridization
reverse transcript PCR for the junction between the transcript of the ETV6-NTRK3 gene fusion.
Murphy and coworkers developed a different two step for identifying the molecular component of MASC. In this two step process a tissue section is (1a) screened with pan-receptor tyrosine kinase antibody (1b) screened with specific receptor tyrosine kinase antibodies known to drive cancers, e.g. TrkC (2) Based on the results of immunohistochemistry, next generation sequencing is used to identify the fusion partner. This assay as come to be called the Trailblaze Pharos assay and is part of an ongoing clinical trial.
In a 2016 report, Skálová and coworkers investigated the discrepancy between positive FISH results and negative reverse transcriptase PCR for the fusion transcript. Using Reverse transcription polymerase chain reaction and a more rigorous nested primer system they found evidence for splice variants of the ETV6-NTRK3 fusion gene. They also presented evidence of a different splice variants led to more aggressive forms of MASC.
