Clinical significance of Myb protein and downstream target genes in salivary adenoid cystic carcinoma

Diana Bell, Dianna Roberts, Matthew Karpowicz, Ehab Y. Hanna, Randal S. Weber, Adel K. El-Naggar

Research output: Contribution to journalArticle

45 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)569-573
Number of pages5
JournalCancer Biology and Therapy
Volume12
Issue number7
DOIs
StatePublished - Oct 1 2011

Fingerprint

Adenoid Cystic Carcinoma
Survival
Genes
Minor Salivary Glands
Neoplasms
Proteins
Gene Fusion
Disease Management
Breast
Transcription Factors
Biomarkers
Epithelial Cells
Immunohistochemistry
Carcinoma
Gene Expression
Therapeutics

Keywords

  • Adenoid cystic carcinoma
  • bcl-2
  • c-kit
  • cox-2

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Molecular Medicine
  • Pharmacology

Cite this

Clinical significance of Myb protein and downstream target genes in salivary adenoid cystic carcinoma. / Bell, Diana; Roberts, Dianna; Karpowicz, Matthew; Hanna, Ehab Y.; Weber, Randal S.; El-Naggar, Adel K.

In: Cancer Biology and Therapy, Vol. 12, No. 7, 01.10.2011, p. 569-573.

Research output: Contribution to journalArticle

Bell, Diana ; Roberts, Dianna ; Karpowicz, Matthew ; Hanna, Ehab Y. ; Weber, Randal S. ; El-Naggar, Adel K. / Clinical significance of Myb protein and downstream target genes in salivary adenoid cystic carcinoma. In: Cancer Biology and Therapy. 2011 ; Vol. 12, No. 7. pp. 569-573.
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