Tumor budding as a novel predictor of occult metastasis in cT2N0 tongue squamous cell carcinoma

Hum Pathol. 2018 Jun:76:1-8. doi: 10.1016/j.humpath.2017.12.021. Epub 2018 Jan 4.

Abstract

Occult neck metastasis is an important prognostic factor in patients with tongue squamous cell carcinoma (TSCC) who are deemed clinically negative for neck metastasis. The purpose of this study was to identify predictive factors for occult neck metastasis arising from TSCC and to determine patient prognosis. Ninety-seven patients with cT2N0 TSCC who underwent surgical resection of their primary lesion as initial therapy were enrolled in this retrospective study. Cutoff values for depth of invasion (≥3.3 mm) and the tumor budding score (≥4) were determined using receiver operator characteristic analyses. Univariate and multivariate analyses revealed that a tumor budding score ≥4 is a significant independent predictive factor for the occurrence of occult neck metastasis, which in turn is a significant independent prognostic factor. When evaluating tumor budding, we demonstrated greater interobserver and intraobserver agreement when using immunohistochemical staining for cytokeratin AE1/AE3 than with hematoxylin and eosin staining (HE). We conclude that the evaluation of tumor budding is effective for identifying populations at high risk of occult neck metastasis, which will enable the planning of appropriate therapeutic strategies for patients with cT2N0 TSCC. Furthermore, cytokeratin staining is recommended over HE staining for simpler and more accurate evaluation of tumor budding.

Keywords: Depth of invasion; Elective neck dissection; Immunohistochemistry; Occult metastasis; Tongue cancer; Tumor budding.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis
  • Cell Movement*
  • Female
  • Glossectomy
  • Head and Neck Neoplasms / chemistry
  • Head and Neck Neoplasms / secondary*
  • Humans
  • Immunohistochemistry
  • Keratins / analysis
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Observer Variation
  • Predictive Value of Tests
  • Reproducibility of Results
  • Retrospective Studies
  • Squamous Cell Carcinoma of Head and Neck / chemistry
  • Squamous Cell Carcinoma of Head and Neck / secondary*
  • Squamous Cell Carcinoma of Head and Neck / surgery
  • Staining and Labeling
  • Tongue Neoplasms / chemistry
  • Tongue Neoplasms / pathology*
  • Tongue Neoplasms / surgery
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • Keratins