CSC^highE-cadherin^low immunohistochemistry panel predicts poor prognosis in oral squamous cell carcinoma

Author(s)

Ortiz, Rafael Carneiro ; Amor, Nadia Ghinelli ; Saito, Luciana Mieli ; Santesso, Mariana Rodrigues ; Lopes, Nathalia Martins ; Buzo, Rodrigo Fonseca ; Fonseca, Angelica Cristina ; Amaral-Silva, Gleyson Kleber ; Moyses, Raquel Ajub ; Rodini, Camila Oliveira

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 14, n. 1, p. 13-pg., 2024-05-08.

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 ALDH1(high) exhibited independent predictive lower survival at the ITF, surpassing the efficacy of traditional tumour staging. Then, specifically at the ITF, profiles characterized by (CSCE)-E-high-cadherin(low) (ALDH1(high)p75NTR(high)E-cadherin(low)) and (CSCE)-E-intermediate-cadherin(low) (ALDH1 or p75NTR(high)E-cadherin(low)) 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 (CSCE)-E-high-cadherin(low) at the ITF of primary tumours, emerges as a preferred prognostic marker closely linked to adverse outcomes in OSCC. (AU)

• FAPESP's process: 13/07245-9 - Investigation of the role of cancer stem cells and microenvironment on epithelial-to-mesenchymal transition, invasion and metastasis in oral squamous cell carcinoma
• Grantee: Camila de Oliveira Rodini Pegoraro
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 15/06945-2 - Differential and comparative immunohistochemical analysis between primary OSCC and corresponding metastatic lesions
• Grantee: Rafael Carneiro Ortiz
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 09/53839-2 - Creation of a Digital Pathology Laboratory using a histological slidescanner
• Grantee: Oslei Paes de Almeida
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 17/25022-8 - Investigation of amoeboid cells in Oral Squamous Cell Carcinoma and their participation on metastasis
• Grantee: Rafael Carneiro Ortiz
• Support Opportunities: Scholarships in Brazil - Doctorate