CRTC1/MAML2 fusion transcript in high grade mucoepidermoid carcinomas of salivary and thyroid glands and Warthin's tumors: Implications for histogenesis and biologic behavior

We analyzed 55 primary salivary gland tumors including 22 mucoepidermoid carcinomas (MECs) to determine the association of MECT1/TORC1/CRTC1-MAML2 fusion transcript to tumor types, level of MEC differentiation and clinicopathologic parameters. Our primary salivary gland tumors were composed of 22 MECs, 11 Warthin's tumors, 10 adenoid cystic carcinomas, two basaloid carcinomas, five salivary duct carcinomas, and five adenocarcinomas, not otherwise specified. We also included, for the first time, three primary MECs of the thyroid gland. We used nested RT-PCR and subsequent sequencing techniques for detection and verification of the fusion transcript in fresh and archival specimens. Eighteen (81%) of the 22 primary salivary and one of the three thyroid glands with MEC were positive for the fusion transcript. The transcript was detected equally in low, intermediate and high grade as well as low and high stage MECs. Significant correlation between fusion negative tumors and distant metastasis was noted (P = 0.005). Four (36%) of the 11 Warthin's tumors were also positive for the transcript. None of the 22 primary non-MEC gland salivary carcinomas were positive for the transcript. We conclude that the CRTC1/ MAML2 transcript may be detected in both low and high grade MEC, that fusion negative tumors may define a subset of biologically aggressive MEC's tumors, that the fusion is present in primary MECs of the thyroid gland and is also detectable in Warthin's tumor, and that a subset of MECs can be targeted for therapeutic intervention.