Tumor-stroma ratio can predict lymph-node metastasis in cT1/2N0 oral tongue squamous cell carcinoma independent of tumor budding grade

Int J Clin Oncol. 2022 Dec;27(12):1818-1827. doi: 10.1007/s10147-022-02249-y. Epub 2022 Oct 5.

Abstract

Background: cT1/2 oral tongue squamous cell carcinoma (OTSCC) often metastasizes to cervical lymph nodes. However, predicting neck lymph-node metastasis (NLM) remains challenging. Pathomorphological evaluation of tumor budding grade (TBG) and tumor-stroma ratio (TSR) reportedly can predict lymph-node metastases. Hence, this study aimed to evaluate TBG and TSR in OTSCC and investigate their relationship to occult NLM and cancer relapse.

Methods: Clinicopathological data of patients with cT1/2N0 OTSCC treated at the University of Tokyo Hospital between 2007 and 2017 were collected. TBG and TSR were evaluated using hematoxylin-eosin staining and cytokeratin AE1/AE3 immunostaining.

Results: Out of 70 patients, 16 underwent elective neck dissection in addition to primary-tumor resection, whereas 54 did not. During follow-up, NLM was found in 35 patients. NLM correlated with the pathological depth of invasion (pDOI) (p < 0.001), TBG (p = 0.008), and TSR (p < 0.001) in univariate analysis and pDOI (p = 0.01) and TSR (p = 0.02) in multivariate analysis. The 5-year recurrence-free survival rate (RFS) was 78% for patients with a pDOI ≤ 5 mm and stroma-poor tumors and 33% for patients with a pDOI > 5 mm and stroma-rich tumors.

Conclusion: Patients with a pDOI > 5 mm and stroma-rich tumors have a high risk for cancer relapse. TSR and pDOI may be promising NLM predictors in cT1/2N0 OTSCC.

Keywords: Depth of invasion; Epithelial–mesenchymal transition; Microenvironment; Tongue cancer; Tumor budding; Tumor–stroma ratio.

MeSH terms

  • Carcinoma, Squamous Cell* / pathology
  • Head and Neck Neoplasms* / pathology
  • Humans
  • Lymphatic Metastasis
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • Prognosis
  • Retrospective Studies
  • Squamous Cell Carcinoma of Head and Neck / pathology
  • Tongue Neoplasms* / pathology
  • Tongue Neoplasms* / surgery