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

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 or (mostly fusions with ) 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 alterations. Reverse-transcription polymerase-chain reaction (RT-PCR) and fluorescence in-situ hybridization (FISH) were performed to detect fusions and 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 and fusions in 10 (27.8%) and 7 (19.4%) ACCs, respectively, in a mutually-exclusive manner. FISH for 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 alterations. Clinicopathologically, a trend of a better disease-specific survival was noted in patients with alterations than in those with fusions and/or strong MYB expression; however, the difference was not significant. Interestingly, we found tumors with alterations significantly frequently occurred in the mandibular regions ( = 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 and alterations. Moreover, the frequent occurrence of -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.