Possible Relationship Between MYBL1 Alterations and Specific Primary Sites in Adenoid Cystic Carcinoma : A Clinicopathological and Molecular Study of 36 Cases

• Published in: YONAGO ACTA MEDICA Vol. 62; no. 1; pp. 67 - 76
• Main Authors: Endo, Yukari, Kuwamoto, Satoshi, Ohira, Takahito, Matsushita, Michiko, Matsushige, Takahiro, Fukuhara, Takahiro, Nakamoto, Shu, Hayashi, Kazuhiko, Kugoh, Hiroyuki, Hirooka, Yasuaki
• Format: Journal Article
• Language: English
• Published: Japan Tottori University Faculty of Medicine 2019
• Subjects: Original; fluorescence in-situ hybridization; mandibular neoplasms; oncogene fusion; adenoid cystic carcinoma; prognosis
• ISSN: 0513-5710; 1346-8049
• DOI: 10.33160/yam.2019.03.010

[ABSTRACT] [Background] Adenoid cystic carcinoma (ACC) is a relatively rare malignant neoplasm that occurs in salivary glands and various other organs. Recent studies have revealed that a significant proportion of ACCs harbor gene alterations involving MYB or MYBL1 (mostly fusions with NFIB) in a mutually-exclusive manner. However, its clinical significance remains to be well-established. [Methods] We investigated clinicopathological and molecular features of 36 ACCs with special emphasis on the significance of MYBL1 alterations. Reverse-transcription polymerase-chain reaction (RT-PCR) and fluorescence in-situ hybridization (FISH) were performed to detect MYB/MYBL1-NFIB fusions and MYBL1 alterations, respectively. Immunohistochemistry was performed to evaluate MYB expression in the tumors. The results were correlated with clinicopathological profiles of the patients. [Results] RT-PCR revealed MYB-NFIB and MYBL1-NFIB fusions in 10 (27.8%) and 7 (19.4%) ACCs, respectively, in a mutually-exclusive manner. FISH for MYBL1 rearrangements was successfully performed in 11 cases, and the results were concordant with those of RT-PCR. Immunohistochemically, strong MYB expression was observed in 23 (63.9%) tumors, none of which showed MYBL1 alterations. Clinicopathologically, a trend of a better disease-specific survival was noted in patients with MYBL1 alterations than in those with MYB-NFIB fusions and/or strong MYB expression; however, the difference was not significant. Interestingly, we found tumors with MYBL1 alterations significantly frequently occurred in the mandibular regions (P = 0.012). Moreover, literature review revealed a similar tendency in a previous study. [Conclusion] Our results suggest that there are some biological or etiological differences between ACCs with MYB and MYBL1 alterations. Moreover, the frequent occurrence of MYBL1-associated ACC in the mandibular regions suggests that MYB immunohistochemistry is less useful in diagnosing ACCs arising in these regions. Further studies are warranted to verify our findings.