Immunohistochemical expression and subcellular localization of β-cateninin in salivary gland malignancies
Journal of Dental School,
Vol. 44 No. 1 (2026),
29 Dey 2025
,
Page e18
https://doi.org/10.22037/jds.v44i1.52088
Abstract
Objective(s): β-catenin is involved in cell-cell adhesion and Wnt signaling pathway, and alterations in its expression or subcellular localization may reflect biological changes in salivary gland malignancies. This study aimed to evaluate the immunohistochemical expression and subcellular localization of β-catenin in selected salivary gland malignancies.
Methods: This retrospective cross-sectional study included 37 archived cases of salivary gland malignancies including mucoepidermoid carcinoma (n=16), adenoid cystic carcinoma (n=14), polymorphous adenocarcinoma (n=4), adenocarcinoma not otherwise specified (n=2), and secretory carcinoma (n=1). β-catenin immunohistochemistry was performed on formalin-fixed paraffin-embedded tissue sections. Staining extent was scored from 0 to 3, and localization was recorded as membranous, membranous/cytoplasmic and nuclear. Data were analyzed using Fisher exact, Kruskal-Wallis, Mann-Whitney U tests, and Bonferroni correction for multiple comparisons.
Results: β-catenin was positive in 35 cases (94.6%), and strong expression was observed in 26 cases (70.3%). Expression scores differed significantly among diagnostic groups (p<0.05); however, after Bonferroni correction, only the difference between mucoepidermoid carcinoma and adenocarcinoma not otherwise specified remained significant (p<0.05). Combined membranous/cytoplasmic staining was most frequent localization pattern (75.7%), followed by membranous staining (18.9%). No nuclear staining was detected. Cellular site of staining was significantly associated with histopathologic diagnosis (p<0.001).
Conclusion: β-catenin may contribute to the pathogenesis and biological behavior of salivary gland malignancies, mainly through changes in its subcellular localization rather than simple positive or negative expression. Cytoplasmic expression may reflect altered adhesion-related function, although the absence of nuclear staining does not support overt canonical Wnt/β-catenin activation in this series.
- β-Catenin
- Salivary Gland Neoplasms
- Immunohistochemistry
- Mucoepidermoid Carcinoma
- Adenoid Cystic Carcinoma
- Wnt Signaling Pathway
How to Cite
References
1. Moghadam SA, Abadi AM, Mokhtari S. Immunohistochemical analysis of CD34 expression in salivary gland tumors. J Oral Maxillofac Pathol. 2015;19(1):30-3. doi:10.4103/0973-029X.157197
2. Neville BW, Damm DD, Allen CM, Chi AC. Oral and Maxillofacial Pathology. 5th ed. St. Louis: Elsevier; 2024. ISBN: 9780323789813.
3. WHO Classification of Tumours Editorial Board. Head and Neck Tumours. 5th ed. Lyon: International Agency for Research on Cancer; 2024. ISBN: 978-92-832-4514-8.
4. Skálová A, Hyrcza MD, Leivo I. Update from the 5th Edition of the World Health Organization Classification of Head and Neck Tumors: Salivary Glands. Head Neck Pathol. 2022;16(1):40-53. doi:10.1007/s12105-022-01420-1
5. Rito M, Fonseca I. Salivary gland neoplasms: does morphological diversity reflect tumor heterogeneity? Pathobiology. 2018;85(1-2):85-95. doi:10.1159/000479070
6. Valenta T, Hausmann G, Basler K. The many faces and functions of beta-catenin. EMBO J. 2012;31(12):2714-36. doi:10.1038/emboj.2012.150
7. Ozawa M, Baribault H, Kemler R. The cytoplasmic domain of the cell adhesion molecule uvomorulin associates with three independent proteins structurally related in different species. EMBO J. 1989;8(6):1711-7. doi:10.1002/j.1460-2075.1989.tb03563.x
8. Clevers H. Wnt/beta-catenin signaling in development and disease. Cell. 2006;127(3):469-80. doi:10.1016/j.cell.2006.10.018
9. Clevers H, Nusse R. Wnt/beta-catenin signaling and disease. Cell. 2012;149(6):1192-205. doi:10.1016/j.cell.2012.05.012
10. Cadigan KM, Waterman ML. TCF/LEFs and Wnt signaling in the nucleus. Cold Spring Harb Perspect Biol. 2012;4(11):a007906. doi:10.1101/cshperspect.a007906
11. Furuse C, Cury PR, Altemani A, Pinto DS Jr, de Araujo NS, de Araujo VC. Beta-catenin and E-cadherin expression in salivary gland tumors. Int J Surg Pathol. 2006;14(3):212-7. doi:10.1177/1066896906290652
12. Chandrashekar C, Angadi PV, Krishnapillai R. Beta-catenin expression in benign and malignant salivary gland tumors. Int J Surg Pathol. 2011;19(4):433-40. doi:10.1177/1066896909346366
13. Batool H, Khan FW, Bashir A, Rafique Z, Mustafa BE, Babar K, et al. Expression of beta-catenin in salivary gland tumors. Cureus. 2024;16(10):e72249. doi:10.7759/cureus.72249
14. Schneider S, Thurnher D, Seemann R, Brunner M, Kadletz L, Ghanim B, et al. The prognostic significance of beta-catenin, cyclin D1 and PIN1 in minor salivary gland carcinoma: beta-catenin predicts overall survival. Eur Arch Otorhinolaryngol. 2016;273(5):1283-92. doi:10.1007/s00405-015-3609-6
15. Wang R, Geng N, Zhou Y, Zhang D, Li L, Li J, et al. 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. 2015;26(Suppl 1):S2145-53. doi:10.3233/BME-151520
16. Zhou CX, Gao Y. Aberrant expression of beta-catenin, Pin1 and cyclin D1 in salivary adenoid cystic carcinoma: relation to tumor proliferation and metastasis. Oncol Rep. 2006;16(3):505-11. doi:10.3892/or.16.3.505
17. Lee CH, Hung YJ, Lin CY, Hung PH, Hung HW, Shieh YS. Loss of SFRP1 expression is associated with aberrant beta-catenin distribution and tumor progression in mucoepidermoid carcinoma of salivary glands. Ann Surg Oncol. 2010;17(8):2237-46. doi:10.1245/s10434-010-0961-z
18. da Costa Miguel MC, Oliveira MC, Seabra FRG, Queiroz LMG, de Almeida Freitas R, de Souza LB. Beta-catenin and cyclin D1 in mucoepidermoid carcinoma of variable histologic grades. Arch Otolaryngol Head Neck Surg. 2005;131(8):701-6. doi:10.1001/archotol.131.8.701
19. Hakata Y, Fukui H, Sekikawa A, Yamagishi H, Ichikawa K, Tomita S, et al. Expression of beta-catenin and REG Ialpha in relation to cell proliferative ability in salivary gland tumors. Exp Ther Med. 2010;1(3):437-43. doi:10.3892/etm_00000068
20. Ferrazzo KL, Neto MM, dos Santos E, dos Santos Pinto D, de Sousa SOM. Differential expression of galectin-3, beta-catenin, and cyclin D1 in adenoid cystic carcinoma and polymorphous low-grade adenocarcinoma of salivary glands. J Oral Pathol Med. 2009;38(9):701-7. doi:10.1111/j.1600-0714.2009.00776.x
21. Park S, Vora M, van Zante A, Humtsoe J, Kim HS, Yom S, et al. Clinicopathologic implications of Myb and beta-catenin expression in adenoid cystic carcinoma. J Otolaryngol Head Neck Surg. 2020;49(1):48. doi:10.1186/s40463-020-00446-1
22. Castle JT, Thompson LDR, Frommelt RA, Wenig BM, Kessler HP. Polymorphous low grade adenocarcinoma: a clinicopathologic study of 164 cases. Cancer. 1999;86(2):207-19. doi:10.1002/(SICI)1097-0142(19990715)86:2<207::AID-CNCR4>3.0.CO;2-Q
23. Skalova A, Vanecek T, Sima R, Laco J, Weinreb I, Perez-Ordonez B, et al. Mammary analogue secretory carcinoma of salivary glands, containing the ETV6-NTRK3 fusion gene. Am J Surg Pathol. 2010;34(5):599-608. doi:10.1097/PAS.0b013e3181d9efcc
24. Chiosea SI, Griffith C, Assaad A, Seethala RR. Clinicopathological characterization of mammary analogue secretory carcinoma of salivary glands. Histopathology. 2012;61(3):387-94. doi:10.1111/j.1365-2559.2012.04232.x
25. Sato M, Yamamoto H, Hatanaka Y, Nishijima T, Jiromaru R, Yasumatsu R, et al. Wnt/beta-catenin signal alteration and its diagnostic utility in basal cell adenoma and histologically similar tumors of the salivary gland. Pathol Res Pract. 2018;214(4):586-92. doi:10.1016/j.prp.2017.12.016
- Abstract Viewed: 12 times
- PDF Downloaded: 5 times