Assessment of CTNNB1 gene mutations and β-catenin immunoexpression in salivary gland pleomorphic adenomas and adenoid cystic carcinomas
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β-Catenin exerts multiple functions in several neoplasms, playing a major role in cell signaling and tumor progression. This study analyzed possible CTNNB1 mutations in salivary gland pleomorphic adenomas (PAs) and adenoid cystic carcinomas (ACCs), and determined possible differences in β-catenin immunoexpression in relation to these mutations, as well as histopathological aspects of these tumors. Twenty-four PAs (15 cell-rich and 9 cell-poor tumors) and 24 ACCs (10 tubular, 8 cribriform, and 6 solid tumors) were selected for the analysis of β-catenin distribution and cellular localization. Furthermore, β-catenin expression was evaluated using the H-score scoring system. Mutations in CTNNB1 exon 3 were investigated by the single-strand conformational polymorphism test. Diffuse β-catenin expression was more frequently observed in ACCs compared to PAs (P = 0.008). No significant difference in β-catenin cellular localization was observed between these tumors (P = 0.098). Comparisons between PA and ACC cases revealed a higher median H-score in the latter (P = 0.036). Cell-rich PAs exhibited a trend for higher H-score than cell-poor tumors (P = 0.060), whereas lower H-scores were observed in cribriform ACCs when compared to tubular and solid ACCs (P = 0.042). Mutations in CTNNB1 were observed in 6 PAs and 7 ACCs, with no significant difference in H-scores for β-catenin according to mutation status (P = 0.135). β-Catenin is important in the pathogenesis of salivary gland PAs and ACCs. In addition, CTNNB1 exon 3 mutations do not seem to significantly influence β-catenin cytoplasmic/membranous expression or nuclear translocation in these tumors.
Keywordsβ-Catenin Salivary gland neoplasm Mutation Immunohistochemistry Pleomorphic adenoma Adenoid cystic carcinoma
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Informed consent was obtained from each patient after approval by the Institutional Ethics Committee on Research Involving Humans.
- 6.Psyrri A, Kotoula V, Fountzilas E, Alexopoulou Z, Bobos M, Televantou D, Karayannopoulou G, Krikelis D, Markou K, Karasmanis I, Angouridakis N, Kalogeras KT, Nikolaou A, Fountzilas G (2014) Prognostic significance of the Wnt pathway in squamous cell laryngeal cancer. Oral Oncol 50:298–305CrossRefPubMedGoogle Scholar
- 8.Bánkfalvi A, Krassort M, Végh A, Felszeghy E, Piffkó J (2002) Deranged expression of the E-cadherin/beta-catenin complex and the epidermal growth factor receptor in the clinical evolution and progression of oral squamous cell carcinomas. J Oral Pathol Med 31(450):7Google Scholar
- 10.Schneider S, Thurnher D, Seemann R, Brunner M, Kadletz L, Ghanim B, Aumayr K, Heiduschka G, Lill C (2016) The prognostic significance of β-catenin, cyclin D1 and PIN1 in minor salivary gland carcinoma: β-catenin predicts overall survival. Eur Arch Otorhinolaryngol 273:1283–1292CrossRefPubMedGoogle Scholar
- 13.Garcia-Rostan G, Camp RL, Herrero A, Carcangiu ML, Rimm DL, Tallini G (2001) Beta-catenin dysregulation in thyroid neoplasms: down-regulation, aberrant nuclear expression, and CTNNB1 exon 3 mutations are markers for aggressive tumor phenotypes and poor prognosis. Am J Pathol 158:987–996CrossRefPubMedPubMedCentralGoogle Scholar
- 15.Ellis GL, Auclair PL (2008) Tumors of the salivary glands. AFIP atlas of tumor pathology. ARP Press, Silver Spring MDGoogle Scholar
- 20.Wang R, Geng N, Zhou Y, Zhang D, Li L, Li J, Ji N, Zhou M, Chen Y, Chen Q (2015) Aberrant Wnt-1/beta-catenin signaling and WIF-1 deficiency are important events which promote tumor cell invasion and metastasis in salivary gland adenoid cystic carcinoma. Biomed Mater Eng 26:S2145–S2153PubMedGoogle Scholar
- 27.Liu Y, Patel L, Mills GB, Lu KH, Sood AK, Ding L, Kucherlapati R, Mardis ER, Levine DA, Shmulevich I, Broaddus RR, Zhang W (2014) Clinical significance of CTNNB1 mutation and Wnt pathway activation in endometrioid endometrial carcinoma. J Natl Cancer Inst 106Google Scholar
- 32.Lee YH, Huang WC, Hsieh MS (2017) CTNNB1 mutations in basal cell adenoma of the salivary gland. J Formos Med Assoc. https://doi.org/10.1016/j.jfma.2017.11.011
- 35.Xu B, Drill E, Ho A, Ho A, Dunn L, Prieto-Granada CN, Chan T, Ganly I, Ghossein R, Katabi N (2017) Predictors of outcome in adenoid cystic carcinoma of salivary glands: a clinicopathologic study with correlation between MYB fusion and protein expression. Am J Surg Pathol 41:1422–1432CrossRefPubMedGoogle Scholar