Exploring the combination of tumor-stroma ratio, tumor-infiltrating lymphocytes, and tumor budding with WHO histopathological grading on early-stage oral squamous cell carcinoma prognosis

Author(s)

Domingues Silva, Gabriela Vivili ; Dolens, Eder da Silva ; Ribeiro Paranaiba, Livia Maris ; Carrinho Ayroza, Ana Lucia ; Gurgel Rocha, Clarissa Araujo ; Almangush, Alhadi ; Salo, Tuula ; Brennan, Peter A. ; Coletta, Ricardo D.

• Document type: Journal article
• Source: JOURNAL OF ORAL PATHOLOGY & MEDICINE; v. N/A, p. 8-pg., 2022-10-03.

Abstract

Background While the relevance of the World Health Organization histopathological grading system as a prognostic tool for oral squamous cell carcinoma has received many critics, other histopathological features such as tumor-stroma ratio, tumor-infiltrating lymphocytes, and tumor budding are displaying promising results. Here, we evaluated the prognostic impact of the incorporation of tumor-stroma ratio, tumor-infiltrating lymphocytes, and tumor budding into World Health Organization histopathological grading for patients with oral squamous cell carcinoma. Methods A total of 95 patients with early-stage oral squamous cell carcinoma were enrolled in the study, and World Health Organization tumor grading, tumor-stroma ratio, tumor-infiltrating lymphocytes, and tumor budding were evaluated in surgical slides stained with hematoxylin and eosin. Survival analyses for cancer-specific survival and disease-free survival were performed using Cox regression models, and receiver operating characteristic curves were applied for assessment of the performance of the combinations. Results Tumor-stroma ratio (stroma-rich) was significantly and independently associated with both shortened cancer-specific survival and poor disease-free survival, individually and in combination with World Health Organization histopathological grading. The combination of tumor-stroma ratio with World Health Organization grading did not improve the discriminatory ability compared to tumor-stroma ratio alone. Although low tumor-infiltrating lymphocytes were associated with shortened cancer-specific survival, the association did not withstand multivariate analysis. However, in combination with World Health Organization grading, low tumor-infiltrating lymphocytes were independently associated with poor cancer-specific survival. The combination of tumor-infiltrating lymphocytes and World Health Organization histopathological grading displayed a better discrimination of poor cancer-specific survival than tumor-infiltrating lymphocytes alone, but not at a significant level. Conclusion Our findings support tumor-stroma ratio as a potential prognostic marker for patients with oral squamous cell carcinoma, and the incorporation of tumor-infiltrating lymphocytes into the World Health Organization grading system improves the prognostic ability of the tumor grading alone. (AU)

• FAPESP's process: 21/13595-9 - Impact of the combination of the histopathological grading system with tumor budding, tumor-stroma ratio and tumor-infiltrating lymphocytes in the prognosis of early-stage oral squamous cell carcinomas.
• Grantee: Gabriela Vivili Domingues Silva
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 18/16077-6 - The prognostic value and biological role of overexpressed proteins in oral squamous cell carcinoma identified by mass spectrometry-based proteomic
• Grantee: Ricardo Della Coletta
• Support Opportunities: Regular Research Grants