Standardised Ki-67 proliferation index assessment in early-stage laryngeal squamous cell carcinoma in relation to local control and survival after primary radiotherapy

Clin Otolaryngol. 2020 Jan;45(1):12-20. doi: 10.1111/coa.13449. Epub 2019 Nov 5.

Abstract

Objectives: Ambiguous results have been reported on the predictive value of the Ki-67 proliferation index (Ki-67 PI) regarding local control (LC) and survival after primary radiotherapy (RT) in early-stage laryngeal squamous cell cancer (LSCC). Small study size, heterogenic inclusion, variations in immunostaining and cut-off values are attributing factors. Our aim was to elucidate the predictive value of the Ki-67 PI for LC and disease-specific survival (DSS) using a well-defined series of T1-T2 LSCC, standardised automatic immunostaining and digital image analysis (DIA).

Methods: A consecutive and well-defined cohort of 208 patients with T1-T2 LSCC treated with primary RT was selected. The Ki-67 PI was determined using DIA. Mann-Whitney U-tests, logistic and Cox regression analyses were performed to assess associations between Ki-67 PI, clinicopathological variables, LC and DSS.

Results: In multivariate Cox regression analysis, poor tumour differentiation (HR 2.20; 95% CI 1.06-4.59, P = .04) and alcohol use (HR 2.84, 95% CI 1.20-6.71; P = .02) were independent predictors for LC. Lymph node positivity was an independent predictor for DSS (HR 3.16, 95% CI 1.16-8.64; P = .03). Ki-67 PI was not associated with LC (HR 1.59; 95% CI 0.89-2.81; P = .11) or DSS (HR 0.98; 95% CI 0.57-1.66; P = .97). In addition, continuous Ki-67 PI was not associated with LC (HR 2.03; 95% CI 0.37-11.14, P = .42) or DSS (HR 0.62; 95% CI 0.05-8.28; P = .72).

Conclusion: The Ki-67 PI was not found to be a predictor for LC or DSS and therefore should not be incorporated in treatment-related decision-making for LSCC.

Keywords: Ki-67; disease-specific survival; head and neck cancer; laryngeal carcinoma; local control; proliferation; radiotherapy.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism
  • Biopsy
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / radiotherapy
  • Female
  • Follow-Up Studies
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / metabolism*
  • Laryngeal Neoplasms / metabolism*
  • Laryngeal Neoplasms / mortality
  • Laryngeal Neoplasms / radiotherapy
  • Male
  • Middle Aged
  • Neoplasm Staging*
  • Netherlands / epidemiology
  • Prognosis
  • Retrospective Studies
  • Survival Rate / trends
  • Time Factors

Substances

  • Biomarkers, Tumor
  • Ki-67 Antigen