title: Clinicopathological significance of the CRTC3-MAML2 fusion transcript in mucoepidermoid carcinoma.
abstract: Mucoepidermoid carcinoma is the most common primary malignancy of the salivary gland. We and others showed that CRTC1-MAML2 gene fusion was associated with favorable clinicopathological tumor features. Recently, a novel gene fusion, CRTC3-MAML2, was reported as a rare gene alteration in a case of mucoepidermoid carcinoma. However, its frequency and clinicopathological significance remains unclear. In all, 101 cases of mucoepidermoid carcinoma and 89 cases of non-mucoepidermoid carcinoma of the salivary gland were analyzed, and RNA was extracted from formalin-fixed, paraffin-embedded specimens. In the CRTC family, there have been three genes, CRTC1, CRTC2, and CRTC3. We developed reverse transcription-polymerase chain reaction (RT-PCR) assays for CRTC1-MAML2, CRTC2-MAML2, and CRTC3-MAML2 fusions. Clinicopathological data of the patients were obtained from their clinical records. Of 101 cases of mucoepidermoid carcinoma, 34 (34%) and 6 (6%) were positive for CRTC1-MAML2 and CRTC3-MAML2 fusion transcripts. However, in the 89 cases of non-mucoepidermoid carcinoma, neither transcript was noted. In the former cases, CRTC1-MAML2 and CRTC3-MAML2 fusions were mutually exclusive. The other fusion, CRTC2-MAML2, was not detected. We confirmed that the clinicopathological features of CRTC1-MAML2-positive mucoepidermoid carcinomas indicated an indolent course. CRTC3-MAML2-positive mucoepidermoid carcinomas also had clinicopathologically favorable features; all cases showed a less advanced clinical stage, negative nodal metastasis, no high-grade tumor histology, and no recurrence or tumor-related death after surgical resection of the tumor. It is interesting to note that patients with CRTC3-MAML2-positive tumors (mean 36 years of age) were significantly younger that those with the CRTC1-MAML2 fusion (55 years) and those with fusion-negative tumors (58 years). In conclusion, CRTC3-MAML2 fusion, which is mutually exclusive with CRTC1-MAML2 fusion and specific to mucoepidermoid carcinoma, may be detected more frequently than previously expected. Mucoepidermoid carcinomas possessing CRTC3-MAML2 fusion may be associated with favorable clinicopathological features and patients may be younger than those with CRTC1-MAML2 fusion or those with no detectable gene fusion.
authors.affiliation: Department of Pathology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan.
authors.forename: Takahisa
authors.initials: T
authors.lastname: Nakayama
authors.forename: Satoru
authors.initials: S
authors.lastname: Miyabe
authors.forename: Mitsukuni
authors.initials: M
authors.lastname: Okabe
authors.forename: Hidenori
authors.initials: H
authors.lastname: Sakuma
authors.forename: Kei
authors.initials: K
authors.lastname: Ijichi
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nagatsuka
authors.forename: Kazuo
authors.initials: K
authors.lastname: Shimozato
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Inagaki
mesh_terms: D000328:Adult; D000367:Age Factors; D018277:Carcinoma, Mucoepidermoid / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D004268:DNA-Binding Proteins / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D050939:Gene Fusion; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012468:Salivary Gland Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D013997:Time Factors; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C500984:CRTC1 protein, human; C493245:CRTC2 protein, human; C495791:CRTC3 protein, human; D004268:DNA-Binding Proteins; C471297:MAML2 protein, human; D009687:Nuclear Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors