Wnt/β-catenin signal alteration and its diagnostic utility in basal cell adenoma and histologically similar tumors of the salivary gland

Abstract

Differential diagnosis among basal cell adenoma (BCA), basal cell adenocarcinoma (BCAC), adenoid cystic carcinoma (ACC) and pleomorphic adenoma (PA) of the salivary gland can be challenging due to their similar histological appearance. Although frequent nuclear β-catenin expression and CTNNB1 mutations have been reported in BCA, further details of the Wnt/β-catenin signal alterations are unclear. The aim of this study was to assess the diagnostic utility of Wnt/β-catenin signal alteration in BCA and morphological mimics. We performed immunohistochemical staining for β-catenin and mutation analysis for Wnt/β-catenin-related genes (CTNNB1, APC, AXIN1 and AXIN2) in BCA (n = 34), BCAC (n = 3), ACC (n = 67) and PA (n = 31). We also analyzed ACC-specific MYB and MYBL1 gene rearrangements by fluorescence in situ hybridization (FISH). Nuclear β-catenin expression (≥3%) was present in 32/34 cases (94.1%) of BCA, and the nuclear β-catenin labeling index was significantly higher than in other tumor types (p = < 0.0001). In BCA, we found mutations in CTNNB1, APC and AXIN1 genes (41.1%, 2.9% and 8.8%, respectively). In BCAC, nuclear β-catenin expression with CTNNB1 mutation was present in 1/3 cases (33.3%). As for ACC, nuclear β-catenin expression was observed in 3/67 cases (4.4%), but all 3 cases harbored either MYB or MYBL1 gene rearrangement. The results suggest that nuclear β-catenin immunoreactivity with appropriate criteria may be helpful to distinguish BCA from histologically similar tumors. However, a minor subset of ACCs with nuclear β-catenin expression require careful diagnosis. In addition, Wnt/β-catenin signal alteration may play a role in the pathogenesis of BCA and BCAC.

Histopathological evaluation of minor salivary gland papillary–cystic tumours: focus on genetic alterations in sialadenoma papilliferum and intraductal papillary mucinous neoplasm

“…In addition to fusion genes resulting from chromosomal rearrangements, certain hotspot mutations of oncogenes are closely linked to particular histological entities, e.g. CTNNB1 mutations in basal cell adenoma/adenocarcinoma, PRKD1 mutations in polymorphous adenocarcinoma, and HRAS mutations in epithelial–myoepithelial carcinoma . The characterisation of the histological and genetic features of minor salivary papillary–cystic tumours leads to an understanding of tumorigenesis and refinement of the tumour classification.…”

Myb Immunohistochemical Staining and Fluorescence in situ Hybridization in Salivary Rare Basaloid Lesions

“…Its nuclear expression was typical and specific for BCA. Sato et al demonstrated that Wnt/β-catenin signal alteration plays a role in the pathogenesis of BCA ( 4 ). Our data showed that all the selected AdCCs in our study had membrane immuno-activity of β-catenin.…”

“…Some studies suggested that β-catenin mutation was present in up to 52% of BCAs. Thus, the corresponding nuclear expression of β-catenin can be detected in BCA and would be a specific marker to identify cBCA or iBCA from AdCC (4). At the same time, few BCAs have incomplete capsules or could have focal capsule invasion, which are easily mistaken as malignant presentation.…”

Analysis of the Clinical Relevance of Histological Classification of Benign Epithelial Salivary Gland Tumours

“…The inner ductal cells typically stain for CK7 but the outer myoepithelial cells are positive for more typical myoepithelial marker such as SMA. p63 and high-molecular weight cytokeratins [81,82] (Fig. 2e, f).…”