Department of Pathology, University of Virginia Health System, Charlottesville, VA 22908-0214, USA.
Mod Pathol. 2011 Sep;24(9):1169-76. doi: 10.1038/modpathol.2011.86. Epub 2011 May 13.
Recent studies have shown that the recurrent t(6;9)(q22-23;p23-24) translocation in adenoid cystic carcinoma results in a novel fusion of the MYB proto-oncogene with the transcription factor gene NFIB. To determine the frequency of this finding, we used RT-PCR assays of the MYB and MYB-NFIB fusion transcripts, and immunohistochemistry for the MYB protein, to study adenoid cystic carcinomas and other epithelial tumors of the salivary glands, and head and neck region. MYB-NFIB fusion transcript was detected in 25 of 29 (86%) frozen adenoid cystic carcinoma tumor samples, and in 14 of 32 (44%) formalin-fixed paraffin-embedded adenoid cystic carcinoma tumor specimens. In contrast, the MYB-NFIB fusion was not expressed in non-adenoid cystic carcinoma neoplasms of the head and neck, confirming the high specificity of the MYB-NFIB fusion. Adenoid cystic carcinomas from various anatomic sites, including salivary gland, sinonasal cavity, tracheobronchial tree, larynx, breast, and vulva were repeatedly fusion-positive, indicating that adenoid cystic carcinomas located in different anatomic sites not only have important morphologic features in common, but also probably evolve through activation of the same molecular pathways. Studies of the expression of MYB revealed that 89% of the tumors, including both fusion-positive and fusion-negative cases, overexpressed MYB RNA. Similarly, 82% of adenoid cystic carcinomas stained positive for MYB protein, compared with 14% of non-adenoid cystic carcinoma neoplasms, indicating that MYB immunostaining may be useful for the diagnosis of adenoid cystic carcinoma, but that neoplasms sometimes in the differential diagnosis are also labeled. The latter are, however, fusion-negative. In summary, our studies show that MYB activation through gene fusion or other mechanisms is a major oncogenic event in adenoid cystic carcinoma occurring at various anatomic sites. In addition to being a diagnostically useful biomarker for adenoid cystic carcinoma, MYB and its downstream effectors are also novel potential therapeutic targets.
最近的研究表明，腺样囊性癌中反复出现的 t(6;9)(q22-23;p23-24)易位导致 MYB 原癌基因与转录因子基因 NFIB 的新型融合。为了确定这一发现的频率，我们使用 MYB 和 MYB-NFIB 融合转录本的 RT-PCR 检测以及 MYB 蛋白的免疫组织化学，研究了唾液腺、头颈部的其他上皮肿瘤和腺样囊性癌。在 29 个冷冻腺样囊性癌肿瘤样本中的 25 个（86%）和 32 个福尔马林固定石蜡包埋的腺样囊性癌肿瘤样本中的 14 个（44%）中检测到 MYB-NFIB 融合转录本。相比之下，MYB-NFIB 融合在头颈部的非腺样囊性癌肿瘤中未表达，证实了 MYB-NFIB 融合的高度特异性。来自不同解剖部位的腺样囊性癌，包括唾液腺、鼻腔鼻窦、气管支气管树、喉、乳腺和外阴，均反复融合阳性，表明位于不同解剖部位的腺样囊性癌不仅具有重要的形态学特征，而且可能通过激活相同的分子途径演变。对 MYB 表达的研究表明，包括融合阳性和融合阴性病例在内的 89%的肿瘤过度表达 MYB RNA。同样，82%的腺样囊性癌对 MYB 蛋白呈阳性染色，而 14%的非腺样囊性癌肿瘤呈阳性染色，表明 MYB 免疫染色可能有助于诊断腺样囊性癌，但有时在鉴别诊断中也会标记肿瘤。然而，后者是融合阴性的。总之，我们的研究表明，通过基因融合或其他机制激活 MYB 是发生在各种解剖部位的腺样囊性癌的主要致癌事件。除了作为诊断有用的标志物外，MYB 及其下游效应物也是新型潜在的治疗靶点。
