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Abstract
Identifying marker combinations for robust prognostic validation in primary tumour compartments remains challenging. We aimed to assess the prognostic significance of CSC markers (ALDH1, CD44, p75NTR, BMI-1) and E-cadherin biomarkers in OSCC. We analysed 94 primary OSCC and 67 metastatic lymph node samples, including central and invasive tumour fronts (ITF), along with clinicopathological data. We observed an increase in ALDH1+/CD44+/BMI-1- tumour cells in metastatic lesions compared to primary tumours. Multivariate analysis highlighted that elevated p75NTR levels (at ITF) and reduced E-cadherin expression (at the tumour centre) independently predicted metastasis, whilst ALDH1high exhibited independent predictive lower survival at the ITF, surpassing the efficacy of traditional tumour staging. Then, specifically at the ITF, profiles characterized by CSChighE-cadherinlow (ALDH1highp75NTRhighE-cadherinlow) and CSCintermediateE-cadherinlow (ALDH1 or p75NTRhighE-cadherinlow) were significantly associated with worsened overall survival and increased likelihood of metastasis in OSCC patients. In summary, our study revealed diverse tumour cell profiles in OSCC tissues, with varying CSC and E-cadherin marker patterns across primary tumours and metastatic sites. Given the pivotal role of reduced survival rates as an indicator of unfavourable prognosis, the immunohistochemistry profile identified as CSChighE-cadherinlow at the ITF of primary tumours, emerges as a preferred prognostic marker closely linked to adverse outcomes in OSCC.
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1 University of São Paulo, Department of Biological Sciences, Bauru School of Dentistry, Bauru, Brazil (GRID:grid.11899.38) (ISNI:0000 0004 1937 0722); University of São Paulo (HRAC/USP), Post-Graduation Program in Rehabilitation Sciences, Hospital for Rehabilitation of Craniofacial Anomalies, São Paulo, Brazil (GRID:grid.11899.38) (ISNI:0000 0004 1937 0722)
2 University of São Paulo, Department of Biological Sciences, Bauru School of Dentistry, Bauru, Brazil (GRID:grid.11899.38) (ISNI:0000 0004 1937 0722)
3 São Paulo State University (UNESP), Department of Surgery and Orthopedics, Faculty of Medicine, Botucatu, Brazil (GRID:grid.410543.7) (ISNI:0000 0001 2188 478X)
4 University of Campinas, Department of Oral Pathology, Piracicaba Dental School, Piracicaba, Brazil (GRID:grid.411087.b) (ISNI:0000 0001 0723 2494)
5 University of São Paulo, Department of Head and Neck Surgery, LIM28, Clinical Hospital HCFMUSP, School of Medicine, São Paulo, Brazil (GRID:grid.11899.38) (ISNI:0000 0004 1937 0722)