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. 2025 Jul 22;15(15):1844.
doi: 10.3390/diagnostics15151844.

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

Drago Boščić  1 , Emili Dragaš  2 , Andro Košec  2   3 , Goran Geber  3 , Čedna Tomasović-Lončarić  4   5 , Davor Vagić  2   3
Affiliations

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

Drago Boščić et al. Diagnostics (Basel). .

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.

Keywords: histopathology; oral squamous cell carcinoma; prognosis; tumor budding; tumor–stroma ratio.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Tumor–stroma ratio (TSR)—tumor area encircled by blue line, >50% stroma content, hematoxylin and eosin stain, magnification 10×.
Figure 2
Figure 2
Tumor–stroma ratio (TSR)—tumor area encircled by blue line, <50% stroma content, hematoxylin and eosin stain, magnification 10×.
Figure 3
Figure 3
Tumor budding (TB)—tumor buds (arrows) defined as single cancer cells and/or clusters of ≤4 cells, hematoxylin and eosin stain, magnification 20×.
Figure 4
Figure 4
Tumor budding (TB)—tumor buds (arrows), positive immunohistochemically for CKAE1/AE3, >5 TB, magnification 20×.
Figure 5
Figure 5
Kaplan–Meier survival curve of follow-up with cumulative survival.
Figure 6
Figure 6
Kaplan–Meier survival curve by T category of the disease.
Figure 7
Figure 7
Kaplan–Meier survival curve by N stage of the disease.
See this image and copyright information in PMC

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