Clinical significance of Myb protein and downstream target genes in salivary adenoid cystic carcinoma
Clinical significance of Myb protein and downstream target genes in salivary adenoid cystic carcinoma
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DOI：
10.4161/cbt.12.7.17008
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发表时间：
2011-10-01
影响因子：
3.6
通讯作者：
El-Naggar, Adel K.
中科院分区：
文献类型：
--
作者：
Bell, Diana;Roberts, Dianna;El-Naggar, Adel K.
腺样囊性癌（ACC），第二个最常见的恶性肿瘤的大和小唾液腺，包括约15-23%的所有癌在这些位置。ACC独特地由双重上皮细胞和肌上皮细胞形成，其产生不同的表型模式。我们推测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。在乳腺、唾液腺、泪腺和耵聍腺的ACC中发现了一种反复发生的t（6;9）（q22-23;p23-24）相互易位，导致包含MYB基因和转录因子NFIB的融合基因伴侣。在融合阳性和部分融合阴性ACC中，Myb蛋白高表达，但Myb蛋白表达的作用及其对下游靶点的影响尚不清楚。为探讨Myb及其下游靶基因（c-kit、考克斯-2、bcl-2）在ACC中的生物学意义和预后意义，我们采用免疫组织化学方法检测了156例ACC中Myb及其下游靶基因的蛋白表达，发现55%的ACC中Myb表达增高，主要局限于肌上皮细胞。我们验证了Myb在一个大的ACC队列（156例患者）中的表达。虽然单个Myb和下游靶点c-kit、bcl-2和考克斯-2对存活没有显著影响，但Myb（+）/c-kit（+）/考克斯-2（+）的组合存活曲线显示比Myb（-）/c-kit（+）/考克斯-2（+）组合更好的存活。Myb可以作为治疗这种疾病的新靶点，未来这些肿瘤的治疗试验可能会更好地基于生物标志物分层和这些肿瘤的细胞组成。
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.