The MECT1-MAML2 Gene Fusion and Benign Warthin's Tumor

Winnes, Marta; Enlund, Fredrik; Mark, Joachim; Stenman, Göran; Fonseca, Isabel; Martins, Conceição; Kaye, Frederic J.

doi:10.2353/jmoldx.2006.060020

Cited by 27 publications

(8 citation statements)

References 21 publications

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“…These observations are in line with previous studies and establish the value of CRTC1/3-MAML2 fusion testing for diagnostic purposes [16,17,32]. This is not only true for the identification of bona fide carcinomas, but also for the differential diagnosis of benign tumors such as oncocytomas and Warthin tumors (MEClike variants) and for certain cystic lesions (congenital or acquired) with mucous metaplasia [13,[33][34][35][36][37][38][39][40]. In the HRC cohort, we noticed three oncocytic MEC variants, one clear cell variant, one Warthin-like variant, and two noninvasive MEC-ex-PA.…”

Section: Discussionsupporting

confidence: 89%

Mucoepidermoid carcinoma of the salivary glands revisited with special reference to histologic grading and CRTC1/3-MAML2 genotyping

et al. 2021

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Mucoepidermoid carcinoma (MEC) is the most common carcinoma of the salivary glands. Here, we have used two large patient cohorts with MECs comprising 551 tumors to study clinical, histological, and molecular predictors of survival. One cohort (n = 167), with known CRCT1/3-MAML2 fusion status, was derived from the Hamburg Reference Centre (HRC; graded with the AFIP and Brandwein systems) and the other (n = 384) was derived from the population-based Cancer Registry of North Rhine-Westphalia (LKR-NRW; graded with the AFIP system). The reliability of both the AFIP and Brandwein grading systems was excellent (n = 155). The weighted kappa for inter-rater agreement was 0.81 (95% CI 0.65–0.97) and 0.83 (95% CI 0.71–0.96) for the AFIP and Brandwein systems, respectively. The 5-year relative survival was 79.7% (95% CI 73.2–86.2%). Although the Brandwein system resulted in a higher rate of G3-MECs, survival in G3-tumors (AFIP or Brandwein grading) was markedly worse than in G1/G2-tumors. Survival in > T2 tumors was markedly worse than in those with lower T-stage. Also, fusion-negative MECs had a worse 5-year progression-free survival. The frequency of fusion-positive MECs in the HRC cohort was 78.4%, of which the majority (86.7%) was G1/G2-tumors. In conclusion, the AFIP and Brandwein systems are useful in estimating prognosis and to guide therapy for G3-MECs. However, their significance regarding young age (≤ 30 years) and location-dependent heterogeneity of in particular G2-tumors is more questionable. We conclude that CRTC1/3-MAML2 testing is a useful adjunct to histologic scoring of MECs and for pinpointing tumors with poor prognosis with higher precision, thus avoiding overtreatment.

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Section: Discussionsupporting

confidence: 89%

Mucoepidermoid carcinoma of the salivary glands revisited with special reference to histologic grading and CRTC1/3-MAML2 genotyping

et al. 2021

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“…Following these reports, several studies have been published describing the specificity of CRTC1–MAML2 rearrangement in cases of MEC, advocating it as a useful diagnostic tool . However, a few authors suggested that CRTC1–MAML2 translocation would also be present in a small subset of Warthin tumor cases , but such evidence has promptly been discharged by recent investigations that failed to identify CRTC1–MAML2 rearrangement in this benign tumor, therefore reinforcing the specificity of this chromosome abnormality in cases of MEC .…”

Section: Crtc1–maml2 Translocation Predicts a Better Prognosis For Pamentioning

confidence: 98%

“…A frequent chromosome rearrangement involving the fusion of exon 1 from a novel gene at 19p13, termed mucoepidermoid carcinoma translocated 1 (MECT1) (also known as CRTC1, TORC1, and WAMTP1), with exons 2–5 of a novel member of the mastermind‐like gene family (MAML2) at 11q21 has been described for MEC cases. The product of this CRTC1–MAML2 translocation was shown to activate transcription of the Notch pathway and of multiple cAMP/CREB target genes, playing a functional role in the development of MEC . Subsequent investigations identified a secondary alternative rearrangement of MAML2 gene this time with CRTC3 gene [t(11,15)(q21;q26)], and the authors concluded that both gene fusions would generate an identical tumor phenotype and play similar roles in the development of the neoplasms affecting not only the salivary glands, but also other anatomic sites .…”

Section: Crtc1–maml2 Translocation Predicts a Better Prognosis For Pamentioning

confidence: 99%

Molecular signature of salivary gland tumors: potential use as diagnostic and prognostic marker

Fonseca

Filho

Altemani

et al. 2015

J Oral Pathology Medicine

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Salivary gland tumors are a highly heterogeneous group of lesions with diverse microscopic appearances and variable clinical behavior. The use of clinical and histological parameters to predict patient prognosis and survival rates has been of limited utility, and the search for new biomarkers that could not only aid in a better understanding of their pathogenesis but also be reliable auxiliaries for prognostic determination and useful diagnostic tools has been performed in the last decades with very exciting results. Hence, gene rearrangements such as CRTC1-MAML2 in mucoepidermoid carcinomas have shown excellent specificity, and more than that, it has been strongly correlated with low-grade tumors and consequently with an increased survival rate and better prognosis of patients affected by neoplasms carrying this translocation. Moreover, MYB-NFIB and EWSR1-ATF1 gene fusions were shown to be specifically found in cases of adenoid cystic carcinomas and hyalinizing clear cell carcinomas, respectively, in the context of salivary gland tumors, becoming reliable diagnostic tools for these entities and potential therapeutic targets for future therapeutic protocols. Finally, the identification of ETV6-NTRK3 in cases previously diagnosed as uncommon acinic cell carcinomas, cystadenocarcinomas, and adenocarcinomas not otherwise specified led to the characterization of a completely new and now widely accepted entity, including, therefore, mammary analogue secretory carcinoma in the list of well-recognized salivary gland carcinomas. Thus, further molecular investigations of salivary gland tumors are warranted, and the recognition of other genetic abnormalities can lead to the acknowledgment of new entities and the acquirement of reliable biomarkers.

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“…The rationale for using p63 in the diagnosis of OMEC is its expression in the epidermoid component of the conventional MEC as opposed to the peripheral staining pattern in oncocytoma and oncocytic carcinomas [ 3 ]. Recently, studies have shown that MECs result from a recurrent t(11,19)(q21;p23) translocation resulting in an MECT1-MAML2 fusion [ 8 ]. This fusion gene can be used to identify and arrive at a diagnosis of MEC in cases where the tumour is composed predominantly of oncocytes [ 9 ].…”

Section: Discussionmentioning

confidence: 99%

Oncocytes in Mucoepidermoid Carcinoma of the Palate: Diagnostic Challenges

Kumar¹,

Natarajan

Sneha

et al. 2017

Case Reports in Dentistry

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The origin of a salivary gland tumour is attributed to cells at various levels of differentiation which present histologically as diverse tissues and cellular patterns. Mitochondria-rich, eosinophilic oncocytes are cells commonly encountered in salivary gland neoplasms. We report a case of mucoepidermoid carcinoma (MEC) in the palate of a 43-year-old female that exhibited a prominent oncocytic component. While the parotid and submandibular glands have been reported as predominant sites for oncocytic MEC (OMEC), the palate and minor salivary glands are rare sites for occurrence. Also, most of the reported cases of OMEC have been histologically of low-grade mucoepidermoid carcinoma with large cystic spaces and good prognosis. In this article, we discuss the differential diagnosis and diagnostic workup of an MEC presenting with oncocytes.

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The MECT1-MAML2 Gene Fusion and Benign Warthin's Tumor

Cited by 27 publications

References 21 publications

Mucoepidermoid carcinoma of the salivary glands revisited with special reference to histologic grading and CRTC1/3-MAML2 genotyping

Mucoepidermoid carcinoma of the salivary glands revisited with special reference to histologic grading and CRTC1/3-MAML2 genotyping

Molecular signature of salivary gland tumors: potential use as diagnostic and prognostic marker

Oncocytes in Mucoepidermoid Carcinoma of the Palate: Diagnostic Challenges

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