# Combined Model of Tumor–Stroma Ratio and Tumor Budding Are Not Associated with Tumor Recurrence or Metastasis in Oral Squamous Cell Carcinoma Patients

**Authors:** Drago Boščić, Emili Dragaš, Andro Košec, Goran Geber, Čedna Tomasović-Lončarić, Davor Vagić

PMC · DOI: 10.3390/diagnostics15151844 · Diagnostics · 2025-07-22

## TL;DR

This study found that combining tumor-stroma ratio and tumor budding does not predict cancer recurrence or metastasis in oral cancer patients.

## Contribution

The study evaluates the TSR/tumor budding model as a novel histological predictor for oral cancer prognosis.

## Key findings

- TSR, tumor budding, and their combined model were not significantly associated with metastasis or recurrence.
- Depth-of-invasion was confirmed as a strong negative prognostic factor.
- TSR and TB correlated with known negative prognostic factors like DOI and T category.

## Abstract

Histopathological grading of oral squamous cell carcinoma is currently based on differentiation of cells, while additional histological parameters, such as the tumor–stroma ratio (TSR), tumor budding (TB), or the combined TSR/tumor budding model could better assess tumor biological behavior and monitoring of patients. Background/Objectives: To integrate risk factors associated with tumor progression: the TSR, TB and TSR/tumor budding model, whose prognostic significance in oral cancer has not yet been evaluated. Methods: An observational cohort retrospective study assembled according to STROBE guidelines on histological materials from 196 patients with invasive squamous cell carcinoma of the oral cavity. The goal of the analysis was to evaluate the association between the tumor stroma ratio, tumor budding, and the combined model of TSR/TB with the clinical and pathologic features of patients with squamous cell carcinoma of the oral cavity and to determine the prognostic value of this model in relation to disease-free survival (DFS) Results: The analysis did not show that the tumor stroma ratio (TSR), tumor budding, and the combined model of TSR/tumor budding were statistically significantly associated with the occurrence of metastatic disease at the start of treatment or during postoperative follow-up, but confirmed the value of depth-of-invasion (DOI) as a negative prognostic factor (HR 15.3, p < 0.001). Conclusions: The TSR, TB, and the combined TSR/TB model were not found to be statistically significant predictors for the disease progression in the Cox regression survival analysis but were found to have a significant correlation with known negative prognostic factors: DOI, neural invasion, and T category.

## Linked entities

- **Diseases:** oral squamous cell carcinoma (MONDO:0004958)

## Full-text entities

- **Diseases:** metastatic disease (MESH:D000092182), Tumor (MESH:D009369), oral cancer (MESH:D009062), Oral Squamous Cell Carcinoma (MESH:D000077195)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12346568/full.md

## References

29 references — full list in the complete paper: https://tomesphere.com/paper/PMC12346568/full.md

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Source: https://tomesphere.com/paper/PMC12346568