Distinctive Patterns of CTNNB1 (beta-Catenin) Alterations in Salivary Gland Basal Cell Adenoma and Basal Cell Adenocarcinoma

作者：Jo Vickie Y; Sholl Lynette M; Krane Jeffrey F

来源：American Journal of Surgical Pathology, 2016, 40(8): 1143-1150.

DOI：10.1097/PAS.0000000000000669

<jats:p>Salivary gland basaloid neoplasms are diagnostically challenging. Limited publications report that some basal cell adenomas harbor <jats:italic toggle="yes">CTNNB1</jats:italic> mutations, and nuclear β-catenin expression is prevalent. We evaluated β-catenin expression in basal cell adenomas and adenocarcinomas in comparison with salivary tumors in the differential diagnosis and performed targeted genetic analysis on a subset of cases. β-catenin immunohistochemistry was performed on formalin-fixed, paraffin-embedded whole sections from 73 tumors. Nuclear staining was scored semiquantitatively by extent and intensity. DNA was extracted from 6 formalin-fixed, paraffin-embedded samples (5 basal cell adenomas, 1 basal cell adenocarcinoma) for next-generation sequencing. Nuclear β-catenin staining was present in 18/22 (82%) basal cell adenomas; most were diffuse and strong and predominant in the basal component. Two of 3 basal cell adenocarcinomas were positive (1 moderate focal; 1 moderate multifocal). All adenoid cystic carcinomas (0/20) and pleomorphic adenomas (0/20) were negative; 2/8 epithelial-myoepithelial carcinomas showed focal nuclear staining. Most β-catenin-negative tumors showed diffuse membranous staining in the absence of nuclear staining. Four of 5 basal cell adenomas had exon 3 <jats:italic toggle="yes">CTNNB1</jats:italic> mutations, all c.104T&gt;C (p.I35T). Basal cell adenocarcinoma showed a more complex genomic profile, with activating mutations in <jats:italic toggle="yes">PIK3CA</jats:italic>, biallelic inactivation of <jats:italic toggle="yes">NFKBIA</jats:italic>, focal <jats:italic toggle="yes">CYLD</jats:italic> deletion, and without <jats:italic toggle="yes">CTNNB1</jats:italic> mutation despite focal β-catenin expression. Nuclear β-catenin expression has moderate sensitivity (82%) for basal cell adenoma but high specificity (96%) in comparison with its morphologic mimics. <jats:italic toggle="yes">CTNNB1</jats:italic> mutation was confirmed in most basal cell adenomas tested, and findings in basal cell adenocarcinoma suggest possible tumorigenic mechanisms, including alterations in PI3K and NF-κB pathways and transcriptional regulation.</jats:p>

• 出版日期2016-8