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

Emiel Kop, Geertruida H. de Bock, Maartje G. Noordhuis, Lorian Slagter-Menkema, Bernard F. A. M. van der Laan, Johannes A. Langendijk, Ed Schuuring, Bert van der Vegt*

*Corresponding author for this work

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ObjectivesAmbiguous 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).

MethodsA 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.

ResultsIn 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).

ConclusionThe 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.

Original languageEnglish
Pages (from-to)12-20
Number of pages9
JournalClinical Otolaryngology
Issue number1
Publication statusPublished - Jan-2020


  • disease-specific survival
  • head and neck cancer
  • Ki-67
  • laryngeal carcinoma
  • local control
  • proliferation
  • radiotherapy
  • CA-IX
  • P53

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