Department of Otorhinolaryngology and Maxillofacial Surgery, Zealand University Hospital, Køge, Denmark.
Department of Otorhinolaryngology Head and Neck Surgery and Audiology, Rigshospitalet, Copenhagen, Denmark.
Mod Pathol. 2018 Aug;31(8):1211-1225. doi: 10.1038/s41379-018-0005-y. Epub 2018 Feb 21.
Adenoid cystic carcinoma is among the most frequent malignancies in the salivary and lacrimal glands and has a grave prognosis characterized by frequent local recurrences, distant metastases, and tumor-related mortality. Conversely, adenoid cystic carcinoma of the breast is a rare type of triple-negative (estrogen and progesterone receptor, HER2) and basal-like carcinoma, which in contrast to other triple-negative and basal-like breast carcinomas has a very favorable prognosis. Irrespective of site, adenoid cystic carcinoma is characterized by gene fusions involving MYB, MYBL1, and NFIB, and the reason for the different clinical outcomes is unknown. In order to identify the molecular mechanisms underlying the discrepancy in clinical outcome, we characterized the phenotypic profiles, pattern of gene rearrangements, and global microRNA expression profiles of 64 salivary gland, 9 lacrimal gland, and 11 breast adenoid cystic carcinomas. All breast and lacrimal gland adenoid cystic carcinomas had triple-negative and basal-like phenotypes, while salivary gland tumors were indeterminate in 13% of cases. Aberrations in MYB and/or NFIB were found in the majority of cases in all three locations, whereas MYBL1 involvement was restricted to tumors in the salivary gland. Global microRNA expression profiling separated salivary and lacrimal gland adenoid cystic carcinoma from their respective normal glands but could not distinguish normal breast adenoid cystic carcinoma from normal breast tissue. Hierarchical clustering separated adenoid cystic carcinomas of salivary gland origin from those of the breast and placed lacrimal gland carcinomas in between these. Functional annotation of the microRNAs differentially expressed between salivary gland and breast adenoid cystic carcinoma showed these as regulating genes involved in metabolism, signal transduction, and genes involved in other cancers. In conclusion, microRNA dysregulation is the first class of molecules separating adenoid cystic carcinoma according to the site of origin. This highlights a novel venue for exploring the biology of adenoid cystic carcinoma.
腺样囊性癌是唾液腺和泪腺最常见的恶性肿瘤之一，预后较差，其特征为频繁局部复发、远处转移和肿瘤相关死亡。相反，乳腺腺样囊性癌是一种罕见的三阴性（雌激素和孕激素受体、HER2）和基底样癌，与其他三阴性和基底样乳腺癌不同，其预后非常好。无论发生部位如何，腺样囊性癌的特征均为涉及 MYB、MYBL1 和 NFIB 的基因融合，而导致不同临床结局的原因尚不清楚。为了确定导致临床结局差异的分子机制，我们对 64 例唾液腺、9 例泪腺和 11 例乳腺腺样囊性癌进行了表型谱、基因重排模式和全局 microRNA 表达谱的特征分析。所有乳腺和泪腺腺样囊性癌均为三阴性和基底样表型，而唾液腺肿瘤有 13%的病例表现为不确定。在所有三个部位的大多数病例中均发现 MYB 和/或 NFIB 异常，而 MYBL1 参与仅限于唾液腺肿瘤。全局 microRNA 表达谱可将唾液腺和泪腺腺样囊性癌与各自的正常腺体区分开来，但不能将正常乳腺腺样囊性癌与正常乳腺组织区分开来。层次聚类将来源于唾液腺的腺样囊性癌与来源于乳腺的腺样囊性癌区分开来，并将泪腺癌置于两者之间。在唾液腺和乳腺腺样囊性癌之间差异表达的 microRNA 的功能注释表明，这些 microRNA 调控参与代谢、信号转导的基因和其他癌症相关基因。总之，microRNA 失调是根据起源部位将腺样囊性癌进行分类的第一类分子。这突出了探索腺样囊性癌生物学的新途径。
