Gene expression patterns in adenoid cystic carcinoma with and without diffuse NOTCH1 intracellular domain (NICD1) immunohistochemistry staining

Lay summary: In this study, we investigated adenoid cystic carcinoma (ACC) and its association with the intracellular domain of NOTCH1 (NICD1) staining patterns. We saw that ACC tumours displaying diffuse NICD1 staining through immunohistochemistry were linked to adverse clinical outcomes, indicating a potential prognostic marker. Using multi-dimensional scaling analysis of RNA data, we observed distinct clustering patterns between ACC tumors with and without diffuse NICD1 staining, underscoring genetic differences between these groups. Interestingly, some ACC tumours lacking diffuse NICD1 staining but with SPEN or TP53 mutations clustered more closely with NICD1-positive ACC. Additionally, we applied the gene expression data to classify ACC into ACC-I and ACC-II subclasses in a separate dataset, although the correlation with NICD1 status was only partially evident. This research reinforces the importance of the molecular heterogeneity of ACC and its potential implications for clinical management.