Prognostic value of CRTC1‐MAML2 translocation in salivary mucoepidermoid carcinoma: Systematic review and meta‐analysis

Pérez‐de‐Oliveira, Maria Eduarda; Wagner, Vivian Petersen; Araujo, André; Martins, Manoela Domingues; Santos‐Silva, Alan Roger; Bingle, Lynne; Vargas, Pablo Agustı́n

doi:10.1111/jop.12970

Cited by 31 publications

(27 citation statements)

References 36 publications

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“…This discrepancy may be explained by several factors, including ambiguity of MEC definition, a low frequency of MEC occurrence and difficulty in differentiating high‐grade MEC from ‘adenosquamous carcinoma’. Recently, a meta‐analysis on this issue has been reported, 46 and supports the prognostic value of the fusions that we showed in this study. To resolve this issue, further studies are warranted.…”

Section: Discussionsupporting

confidence: 90%

Clinicopathological significance of EGFR pathway gene mutations and CRTC1/3–MAML2 fusions in salivary gland mucoepidermoid carcinoma

et al. 2020

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Aims Mucoepidermoid carcinoma (MEC) is one of the most common salivary gland carcinomas. Epidermal growth factor receptor (EGFR) signalling pathway gene mutations are important in predicting a patient’s prognosis, selecting molecularly targeted drugs and estimating the efficacy of a molecular therapy. However, their significance in MEC have been poorly clarified. CRTC1/3–MAML2 fusions are specific to MEC and may be associated with favourable characteristics in these patients. Methods and results We looked for CRTC1/3–MAML2 fusions and gene alterations in the EGFR, RAS family (KRAS, HRAS and NRAS), PIK3CA, BRAF and AKT1 in 101 MEC cases. We also examined mutations in TP53. CRTC1/3–MAML2 fusions were found in 62.4% of the cases. KRAS, HRAS and PIK3CA mutations were detected in 6.9%, 2.0% and 6.9%, respectively, but other EGFR pathway genes were not mutated. In total, gene mutations (RAS/PIK3CA) in the EGFR pathway were detected in 14.9% of the cases. TP53 mutations were found in 20.8%. CRTC1/3–MAML2 fusions were associated with a better prognosis and RAS/PIK3CA mutations a worse prognosis of the patients, respectively, and both were selected as independent prognostic factors for the overall survival of the patients. TP53 mutations had no prognostic impact. CRTC1/3–MAML2 fusion‐positive rates were inversely associated with the patients’ age and the fusions were found in 82% of patients aged < 30 years. Conclusions RAS/PIK3CA mutations were frequently detected, and may be a biomarker for a poorer prognosis in MEC patients. CTRC1/3–MAML2 fusions were positive in most of the young MEC patients.

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Section: Discussionsupporting

confidence: 90%

Clinicopathological significance of EGFR pathway gene mutations and CRTC1/3–MAML2 fusions in salivary gland mucoepidermoid carcinoma

et al. 2020

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“…The survival of fusion‐positive patients has always been and consistently better than that of fusion‐negative patients in any study conducted, including those reports that concluded that the fusions had no prognostic significance 21‐23 . A recent meta‐analysis study supports the association of CRTC1/3‐MAML2 fusions with a favorable outcome for the patients 19 . In patients with fusion‐positive MEC tumors, tumor recurrence might not directly indicate a poor OS.…”

Section: Discussionmentioning

confidence: 99%

“…There has been debate regarding the prognostic value of CRTC1/3‐MAML2 fusions. Many studies have reported that MEC patients with these fusions had a significantly better survival than those without the fusions 7,11,13‐19 . In addition, it has become widely accepted that fusion‐positive MEC tumors are associated with favorable clinicopathologic and molecular features 16,35,36 .…”

Section: Discussionmentioning

confidence: 99%

“…Subsequently, several other studies also reported a survival advantage for CRTC1/3‐MAML2 fusions in patient groups of comparable or smaller size 7,14‐18 . A recent meta‐analysis for the prognostic significance of the fusions supports the above findings 19 . However, some research groups have reported an opposing conclusion as to the prognostic significance of CRTC1/3‐MAML2 fusions in salivary gland MEC in patient groups of comparable or smaller size 20‐23 …”

Section: Introductionmentioning

confidence: 88%

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Prognostic impact of CRTC1/3‐MAML2 fusions in salivary gland mucoepidermoid carcinoma: A multiinstitutional retrospective study

et al. 2020

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Mucoepidermoid carcinoma (MEC) is rare, but the most common primary malignancy of the salivary gland and not infrequent in young individuals. CRTC1/3‐MAML2 fusions are frequently detected in MEC and are useful as a diagnostic biomarker. However, there has been debate as to whether the fusions have prognostic significance. In this study, we retrospectively collected 153 salivary gland MEC cases from 11 tertiary hospitals in Japan. As inclusion criteria, the MEC patients in this study had curative surgery as the initial treatment, received no preoperative treatment, and had no distant metastasis at the time of the initial surgery. The MEC diagnosis was validated by a central pathology review by five expert salivary gland pathologists. The CRTC1/3‐MAML2 fusions were detected using FISH and RT‐PCR. In 153 MEC cases, 90 (58.8%) were positive for CRTC1/3‐MAML2 fusions. During the follow‐up period, 28 (18.3%) patients showed tumor recurrence and 12 (7.8%) patients died. The presence of the fusions was associated with favorable tumor features. Of note, none of the fusion‐positive patients died during the follow‐up period. Statistical analysis showed that the presence of the fusions was a prognostic indicator of a better overall survival in the total and advanced‐stage MEC cohorts, but not in the early‐stage MEC cohort. In conclusion, CRTC1/3‐MAML2 fusions are an excellent biomarker for favorable overall survival of patients with salivary gland MEC.

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“…Molecular analyses of these tumors have identified the t(11:19)(q21;p13) translocation in MEC. The t(11:19)(q21;p13) translocation results in a fusion oncogene, CRTC1‐MAML2, which appears to be related to the prognosis of salivary MEC 5‐7 . Additionally, they were identified cases with a t(6;22)(p21;q12) translocation resulting in an EWSR1‐POU5F1 gene fusion present in high‐grade MEC 8 .…”

Section: Introductionmentioning

confidence: 99%

DNA methyltransferase expression is associated with cell proliferation in salivary mucoepidermoid carcinoma

Guimarães

Almeida

Castilho

et al. 2020

J Oral Pathology Medicine

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Objectives The present study investigated the correlation between the expression of DNA methyltransferase (DNMT)1, DNMT3A, and DNMT3B and the proliferation of mucoepidermoid carcinomas (MECs) using the molecular markers Ki‐67 and cyclin D1. This study also demonstrates the effects of 5‐aza‐2‐deoxycytidine (5AC) on the MEC tumor cell lines in relation to DNMT1 and DNMT3A expression, and cell‐cycle arrest. Materials and Methods The immunohistochemistry of DNMT1, DNMT3A, DNMT3B, Ki‐67, and cyclin D1 was analyzed in 40 samples of MEC and 15 samples of healthy minor salivary glands. The effects of 5AC on DNMT1 and DNMT3B expression in MEC cell lines were analyzed by Western blot, and the effects of 5AC on the cell cycle were analyzed using flow cytometry. Results The expression of DNMT1 and DNMT3B was more intense in MECs than in healthy salivary glands. A strong correlation was found between the expression of the DNMTs and the proliferation markers. This correlation was validated In Vitro, where treatment with 5AC reduced the expression of the DNMTs and the percentage of cells at the G2/M phase of the cell cycle. Conclusion The expression of DNMT1, DNMT3A, DNMT3B is correlated significantly with the expression of Ki‐67 and cyclin D1. The treatment with 5AC reduces DNMT expression and decreases the percentage of cells at the G2/M phase of the cell cycle, while increasing the cells at the G0/G1 phase.

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Prognostic value of CRTC1‐MAML2 translocation in salivary mucoepidermoid carcinoma: Systematic review and meta‐analysis

Cited by 31 publications

References 36 publications

Clinicopathological significance of EGFR pathway gene mutations and CRTC1/3–MAML2 fusions in salivary gland mucoepidermoid carcinoma

Clinicopathological significance of EGFR pathway gene mutations and CRTC1/3–MAML2 fusions in salivary gland mucoepidermoid carcinoma

Prognostic impact of CRTC1/3‐MAML2 fusions in salivary gland mucoepidermoid carcinoma: A multiinstitutional retrospective study

DNA methyltransferase expression is associated with cell proliferation in salivary mucoepidermoid carcinoma

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