Prognostic and Clinicopathological Significance of the Aberrant Expression of β-Catenin in Oral Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis

SIMPLE SUMMARY: β-catenin is a multifunctional protein whose physiological functions are mainly related to the maintenance of cell-cell adhesion by forming complexes with the adhesion molecule E-cadherin, both responsible for the preservation of squamous epithelia homeostasis. The loss of β-catenin expression in the cell membrane, the failure of cytoplasmic degradation mechanisms—essentially related to the activation of Wnt canonical oncogenic pathway—and/or its translocation to the nucleus—developing actions as a transcription factor of oncogenes—are aberrant mechanisms with oncogenic implications in oral carcinogenesis. In this systematic review and meta-analysis on 41 studies and 2746 oral squamous cell carcinoma (OSCC) patients we demonstrate that the aberrant expression of β-catenin—mainly the immunohistochemical analysis of its loss in the cell membrane—behaves as a prognostic biomarker, significantly associated with poor survival, essentially linked to the increased risk for the development of lymph node metastases, higher tumour size and clinical stage in these patients. ABSTRACT: This systematic review and meta-analysis aims to evaluate the prognostic and clinicopathological significance of the aberrant expression of β-catenin (assessed through the immunohistochemical loss of membrane expression, cytoplasmic and nuclear expression) in oral squamous cell carcinoma (OSCC). We searched for primary-level studies published before October-2021 through PubMed, Embase, Web of Science, Scopus, and Google Scholar, with no limitation in regard to their publication date or language. We evaluated the methodological quality and risk of bias of the studies included using the QUIPS tool, carried out meta-analyses, explored heterogeneity and their sources across subgroups and meta-regression, and conducted sensitivity and small-study effects analyses. Forty-one studies (2746 patients) met inclusion criteria. The aberrant immunohistochemical expression of β-catenin was statistically associated with poor overall survival (HR = 1.77, 95% CI = 1.20–2.60, p = 0.004), disease-free survival (HR = 2.44, 95% CI = 1.10–5.50, p = 0.03), N+ status (OR = 2.39, 95% CI = 1.68–3.40, p < 0.001), higher clinical stage (OR = 2.40, 95% CI = 1.58–3.63, p < 0.001), higher tumour size (OR = 1.76, 95% CI = 1.23–2.53, p = 0.004), and moderately-poorly differentiated OSCC (OR = 1.57, 95% CI = 1.09–2.25, p = 0.02). The loss of β-catenin in the cell membrane showed the largest effect size in most of meta-analyses (singularly for poor overall survival [HR = 2.37, 95% CI = 1.55–3.62, p < 0.001], N+ status [OR = 3.44, 95% CI = 2.40–4.93, p < 0.001] and higher clinical stage [OR = 2.51, 95% CI = 1.17–5.35, p = 0.02]). In conclusion, our findings indicate that immunohistochemical assessment of the aberrant expression of β-catenin could be incorporated as an additional and complementary routine prognostic biomarker for the assessment of patients with OSCC.