Prognostic significance of 1p36 locus deletion in adenoid cystic carcinoma of the salivary glands

Abstract

Adenoid cystic carcinoma (AdCC) of the salivary glands is characterized by MYB-NFIB or MYBL1-NFIB fusion, prolonged but relentlessly progressive clinical course with frequent recurrences, and development of distant metastasis resulting in high long-term mortality. Currently, no effective therapy is available for patients with advanced non-resectable and/or metastatic disease. Complicating the clinical management of this patient group is the lack of prognostic markers. The purpose of this study is to investigate the prognostic value of 1p36 loss in patients with AdCC. The presence of 1p36 deletion and gene fusions involving the MYB, NFIB, and MYBL1 genes in a cohort of 93 salivary gland AdCCs was studied using fluorescence in situ hybridization. These results were statistically correlated with clinical data and outcome. Deletion of 1p36 in AdCC was identified in 13 of 85 analyzable cases (15.29%). MYB-NFIB fusion was detected in 57/85 (67.1%), MYBL1-NFIB fusion in 12/85 (14.1%), MYB-X fusion in 4/85 (4.7%), MYBL1-X in 4/85 (4.7%), and NFIB-X in 2/85 (2.4%) of AdCC cases. None of the 1p36-deleted samples showed MYBL1 rearrangement. Statistical analysis demonstrated a significant correlation between 1p36 deletion and advanced tumor stage and solid histology (p = 0.0061 and 0.0007, respectively). Kaplan-Meier survival curves showed statistically significant correlations between 1p36 deletion and decreased overall survival, disease-specific survival, recurrence-free interval, and recurrence-free survival, all of which were maintained in multivariate analysis. We demonstrate that 1p36 deletion can serve as an indicator of unfavorable outcome of patients with salivary gland AdCC.

LAPTM4B‑35 expression is associated with pathological grades and clinical stages in salivary adenoid cystic carcinoma

“…Overall, SACC exhibit a low mutational burden. Deletion of the chromosomal region 1p36 has been identified predominantly in solid type ACC and was associated with an aggressive clinical course (21). NOTCH1 mutations were identified in a subgroup of patients with solid subtype, advanced-stage disease and poor prognosis.…”

Molecular features of adenoid cystic carcinoma with an emphasis on microRNAexpression

“…However, in contrast to more common malignancies, only very few molecular‐based prognostic studies have been carried out in salivary gland ACC. Among the most interesting is that deletion of the chromosomal region 1p32‐36 is associated with an aggressive clinical course and occurs predominantly in solid‐type ACC . The SPEN gene, a negative regulator of Notch signaling, is located to 1p36, and Notch signaling is known to be especially active in solid‐type ACC .…”

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

“…Several clinicopathologic parameters are of prognostic value in ACC, including involved surgical margins, vascular invasion, solid histology, and high stage . Only few molecular markers have been shown to be of independent prognostic value in salivary gland carcinomas, mainly 1p36 deletion in ACC and CDKN2A deletion in MEC .…”

“…including involved surgical margins, vascular invasion, solid histology, and high stage (51). Only few molecular markers have been shown to be of independent prognostic value in salivary gland carcinomas, mainly 1p36 deletion in ACC and CDKN2A deletion in MEC (52)(53)(54). Some general differences in clinical course between tumor types can be discerned with cervical lymph node metastases being frequent in SDC, in contrast to local and distant metastases being the hallmarks of ACC.…”