Limited additive value of the Ki-67 proliferative index on patient survival in World Health Organization-classified pulmonary carcinoids

Dorian R. A. Swarts, Martina Rudelius, Sandra M. H. Claessen, Jack P. Cleutjens, Stefan Seidl, Marco Volante, Frans C. S. Ramaekers, Ernst J. M. Speel*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

31 Citations (Web of Science)


Aims: Currently pulmonary carcinoids are separated into typical and atypical based on mitotic count and presence of necrosis, according to the World Health Organization. At variance with gastroenteropancreatic neuroendocrine tumours, which are graded based on mitotic count and Ki-67 proliferative index, the use of Ki-67 for grading pulmonary carcinoids is still under debate.

Methods and results: In this study we evaluated the prognostic impact of Ki-67 assessment in a multicentre cohort of 201 carcinoids [147 typical carcinoids (TCs) and 54 atypical carcinoids (ACs)] using manual analysis (2000 cells counted) and digital image analysis (in-house Leica Qwin program; >= 4500 cells counted). The Ki-67 proliferative index was correlated with overall survival by means of univariate analysis and in comparison to clinical data by means of multivariable analysis. The Ki-67 index was significantly higher in ACs than in TCs for both counting methods (P

Conclusions: Our study demonstrates that, although Ki-67 is a strong prognostic factor for pulmonary carcinoids, its usefulness in addition to histopathology in prediction of prognosis is limited. None the less, it may have additional value, especially in cases that are difficult to classify, in combination with histopathology and other molecular markers.

Original languageEnglish
Pages (from-to)412-422
Number of pages11
Issue number3
Publication statusPublished - Feb 2017


  • histopathology
  • Ki-67 proliferative index
  • MIB-1
  • prognosis
  • pulmonary carcinoids
  • LUNG

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