Adenoid cystic carcinomas of the salivary gland, lacrimal gland, and breast are morphologically and genetically similar but have distinct microRNA expression profiles

Abstract

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.

Extracellular Vesicles: New Endogenous Shuttles for miRNAs in Cancer Diagnosis and Therapy?

“…In addition, to explain the differences in clinical behavior between adenoid cystic carcinoma of the salivary gland, lacrimal gland, and breast, Andreasen et al characterized the global miRNA expression profile in these types of cancer. The authors showed that miRNA expression profiling distinguishes these tumors based on the site of origin and that differentially expressed miRNAs are involved in the regulation of cellular processes that could be responsible for a more aggressive clinical course in tumor relative to those with better prognosis [114].…”

Molecular and Cellular Modelling of Salivary Gland Tumors Open New Landscapes in Diagnosis and Treatment

“…Strong parallelisms exist between the chromosomal rearrangements at the basis of different glandular tumors. Particularly, gene fusion involving MYB, MYBL1, and NFIB have been described in salivary, lacrimal, and triple-negative mammary AdCC, although the clinical outcome of these tumors can greatly vary [ 87 ]. Chromosomal loss such as depletion of the regions 6q23–q27, 12q12–q14, and 1p32–p36 are also common in AdCC, with the latter occurring in 44% of cases and are linked to shorter survival rates [ 88 ].…”

An update on head and neck cancer: new entities and their histopathology, molecular background, treatment, and outcome

“…Through recent years, a network of fusion genes, hotspot mutations, and copy‐number alterations has been shown to underpin a large number of different tumor types, most of which have subsequently been identified in their histological counterparts in the breast and lacrimal gland (Table ; ). Most are known from cancers in other sites, but a few are found exclusively in specific types of salivary gland carcinomas.…”

“…Through recent years, a network of fusion genes, hotspot mutations, and copy-number alterations has been shown to underpin a large number of different tumor types, most of which have subsequently been identified in their histological counterparts in the breast and lacrimal gland ( Table 1; 8,9,[30][31][32][33][34].…”