Clinicopathological significance of the CRTC3-MAML2 fusion transcript in mucoepidermoid carcinoma

Takahisa Nakayama, Satoru Miyabe, Mitsukuni Okabe, Hidenori Sakuma, Kei Ijichi, Yasuhisa Hasegawa, Hitoshi Nagatsuka, Kazuo Shimozato, Hiroshi Inagaki

Research output: Contribution to journalArticle

79 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1575-1581
Number of pages7
JournalModern Pathology
Volume22
Issue number12
DOIs
Publication statusPublished - Dec 2009

Fingerprint

Mucoepidermoid Carcinoma
Gene Fusion
Neoplasms
Salivary Glands
Carcinoma
Paraffin
Formaldehyde
Genes
Reverse Transcription
Histology
RNA
Neoplasm Metastasis
Recurrence
Polymerase Chain Reaction

Keywords

  • Clinicopathological study
  • CRTC3?MAML2 fusion
  • Mucoepidermoid carcinoma
  • Prognosis

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Nakayama, T., Miyabe, S., Okabe, M., Sakuma, H., Ijichi, K., Hasegawa, Y., ... Inagaki, H. (2009). Clinicopathological significance of the CRTC3-MAML2 fusion transcript in mucoepidermoid carcinoma. Modern Pathology, 22(12), 1575-1581. https://doi.org/10.1038/modpathol.2009.126

Clinicopathological significance of the CRTC3-MAML2 fusion transcript in mucoepidermoid carcinoma. / Nakayama, Takahisa; Miyabe, Satoru; Okabe, Mitsukuni; Sakuma, Hidenori; Ijichi, Kei; Hasegawa, Yasuhisa; Nagatsuka, Hitoshi; Shimozato, Kazuo; Inagaki, Hiroshi.

In: Modern Pathology, Vol. 22, No. 12, 12.2009, p. 1575-1581.

Research output: Contribution to journalArticle

Nakayama, T, Miyabe, S, Okabe, M, Sakuma, H, Ijichi, K, Hasegawa, Y, Nagatsuka, H, Shimozato, K & Inagaki, H 2009, 'Clinicopathological significance of the CRTC3-MAML2 fusion transcript in mucoepidermoid carcinoma', Modern Pathology, vol. 22, no. 12, pp. 1575-1581. https://doi.org/10.1038/modpathol.2009.126
Nakayama, Takahisa ; Miyabe, Satoru ; Okabe, Mitsukuni ; Sakuma, Hidenori ; Ijichi, Kei ; Hasegawa, Yasuhisa ; Nagatsuka, Hitoshi ; Shimozato, Kazuo ; Inagaki, Hiroshi. / Clinicopathological significance of the CRTC3-MAML2 fusion transcript in mucoepidermoid carcinoma. In: Modern Pathology. 2009 ; Vol. 22, No. 12. pp. 1575-1581.
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