title: Clinical significance of Myb protein and downstream target genes in salivary adenoid cystic carcinoma.
abstract: Adenoid cystic carcinoma (ACC), the second most frequent malignancy of the major and minor salivary glands, comprise of approximately 15-23% of all carcinomas at these locations. ACC is uniquely formed of dual epithelial and myoepithelial cells that give rise to different phenotypic patterns. We hypothesize that the dual myoepithelial/ epithelial composition of ACCs underlie their biological heterogeneity and may impact on their therapeutic management. A recurrent reciprocal translocation of t(6;9)(q22-23; p23-24) resulting in fusion gene partners comprising MYB gene the transcription factor NFIB has been reported in ACC of breast, salivary, lachrymal and ceruminal glands. In fusion positive and a subset of fusion negative ACCs, high expression of the transcript Myb was found. However, the role of Myb protein expression and the potential effect on the downstream targets have not been investigated. To investigate the biological and prognostic significance of use of elevated levels of Myb and its downstream target genes (c-kit, cox-2, bcl-2), we analyzed, by immunohistochemistry, the protein expression of these genes in 156 ACCs. We have found that 55% of ACCs have increased Myb expression mainly confined to myoepithelial cells. We validated Myb expression on a large cohort of ACCs (156 patients). Although no significant effects of the individual Myb and downstream targets c-kit, bcl-2 and cox-2 on survival was noticed, the combinations survival curve for Myb+/c-kit+/cox-2+ showed better survival than combination Myb-/c-kit+/cox-2+. Myb may serve as a new target for the management of this disease, and future therapeutic trials of these tumors may be better based on biomarker stratification and the cellular composition of these tumors.
authors.affiliation: Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Bell
authors.forename: Dianna
authors.initials: D
authors.lastname: Roberts
authors.forename: Matthew
authors.initials: M
authors.lastname: Karpowicz
authors.forename: Ehab Y
authors.initials: EY
authors.lastname: Hanna
authors.forename: Randal S
authors.initials: RS
authors.lastname: Weber
authors.forename: Adel K
authors.initials: AK
authors.lastname: El-Naggar
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003528:Carcinoma, Adenoid Cystic / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D015331:Cohort Studies; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics* / Q000378:metabolism; D012468:Salivary Gland Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D055815:Young Adult
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D020598:Proto-Oncogene Proteins c-myb; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D019009:Proto-Oncogene Proteins c-kit