Prognostic value of E-cadherin, syndecan-2, and cyclin D1 immunohistochemistry in minor salivary gland adenoid cystic carcinoma: A cohort study.

BackgroundAdenoid cystic carcinoma (ACC) of the salivary glands has a poor long-term prognosis. Independent prognostic factors of ACC include histological and clinicopathological features, while a validated gold-standard prognostic immunohistochemical markers are still lacking. Functions of cell adhesion molecule E-cadherin which maintain epithelial integrity, and cell cycle and function regulators nuclear protein Cyclin D1 and transmembrane heparan sulfate proteoglycan syndecan-2 in ACC have not been studied.ObjectiveThe aim of this study was to investigate the immunohistochemical expression of E-cadherin, syndecan-2, and cyclin D1 in ACC of the minor salivary glands. Our objective was to evaluate the prognostic relevance of these markers in relation to disease progression and patient outcomes.MethodsThis retrospective study included 46 patients with minor salivary gland ACC treated at the Department of Otorhinolaryngology-Head and Neck Surgery, Helsinki University Hospital, Finland, between 1974 and 2012. Formalin-fixed paraffin-embedded tumor tissue samples were used for immunohistochemical analysis. Staining intensity was scored and associated with clinicopathological parameters and survival data.ResultsImmunopositivity varied among tumors, sometimes exhibiting heterogeneous expression within the same tumor. We found moderate to high E-cadherin expression to significantly associate with improved overall (p = 0,024) and disease-specific survival (p = 0.005). Additionally in multivariate analysis, moderate to high E-cadherin associated with better disease-specific survival with hazard ratio of 0.219 (95% CI 0.065-0.734, p = 0.014). Notably, all four patients with neck recurrences demonstrated low syndecan-2 positivity (p = 0.023). Cyclin D1 did not associate significantly with survival.ConclusionsIn conclusion, all the studied markers were expressed in the minor salivary gland ACC. E-cadherin showed potentiality as a prognostic immunohistochemical biomarker for survival analysis. Low syndecan-2 expression may be indicative for regional recurrence. Validation in larger multicenter cohorts is warranted to confirm these observations.