Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Cancer Biol Ther. 2011 Oct 1;12(7):569-73. doi: 10.4161/cbt.12.7.17008.
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.
腺样囊性癌（ACC）是大、小唾液腺第二常见的恶性肿瘤，约占这些部位所有癌的 15-23%。ACC 由双重上皮和肌上皮细胞组成，这些细胞产生不同的表型模式。我们假设 ACC 的双重肌上皮/上皮组成是其生物学异质性的基础，并可能影响其治疗管理。已经报道了在乳腺、唾液腺、泪腺和耵聍腺的 ACC 中存在 t(6;9)(q22-23;p23-24)的反复相互易位，导致包含转录因子 NFIB 的 MYB 基因的融合基因伴侣。在融合阳性和一部分融合阴性的 ACC 中，发现转录本 Myb 的高表达。然而，Myb 蛋白表达的作用及其对下游靶标的潜在影响尚未被研究。为了研究 Myb 及其下游靶基因（c-kit、cox-2、bcl-2）升高水平的生物学和预后意义，我们通过免疫组织化学分析了 156 例 ACC 中这些基因的蛋白表达。我们发现 55%的 ACC 存在 Myb 表达增加，主要局限于肌上皮细胞。我们在一个大型 ACC 队列（156 例患者）中验证了 Myb 的表达。虽然个别 Myb 和下游靶基因 c-kit、bcl-2 和 cox-2 对生存的影响没有统计学意义，但 Myb+/c-kit+/cox-2+的组合生存曲线显示出比 Myb-/c-kit+/cox-2+更好的生存。Myb 可能成为治疗这种疾病的新靶点，未来对这些肿瘤的治疗试验可能更好地基于生物标志物分层和这些肿瘤的细胞组成。
