The use of Ki-67 labeling index to grade pulmonary well-differentiated neuroendocrine neoplasms: current best evidence

Mod Pathol. 2018 Oct;31(10):1523-1531. doi: 10.1038/s41379-018-0076-9. Epub 2018 May 25.

Abstract

Although Ki-67 labeling index (Ki-67%) is not a diagnostic or grading criterion in the World Health Organization classification of pulmonary carcinoid tumor, oncologists often request this test. A survey was administered at a North American Society for Neuroendocrine Tumors meeting to understand how Ki-67% is used in oncologic practices. A systematic literature review was performed to gather best evidence regarding the use of Ki-67%. Consecutive pulmonary carcinoids were stratified into pulmonary typical carcinoids with Ki-67% <5% (group A, n = 187), typical carcinoids with Ki-67% ≥5% (group B, n = 38) and atypical carcinoids irrespective of Ki-67% (group C, n = 31). Overall survival, progression-free survival, recurrence proportions and time to recurrence were compared, by group, using the log-rank test, chi-square statistics and ANOVA, respectively. Our survey confirmed that Ki-67% is frequently used by specialists caring for these patients. Ki-67% of 1-7% significantly correlated with overall survival in the literature but we found no information about Ki-67% cut-off values that would accurately distinguish pulmonary typical from atypical carcinoids or estimate the prognosis of patients stratified by World Health Organization diagnosis and Ki-67% cut-off. Overall survival was significantly different in our 3 patient groups (p < 0.001), with survival probabilities decreasing from groups A to C. Progression-free survival was significantly longer in group A than B (p < 0.007). Our results support the concept that by combining World Health Organization diagnosis and Ki-67%, pulmonary carcinoids can be stratified into 3 grades: G1 (typical carcinoids with Ki-67% <5), G2 (typical carcinoids with Ki-67% ≥5%) and G3 (atypical carcinoids) with different prognoses.

Publication types

  • Systematic Review

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / analysis
  • Carcinoid Tumor / classification
  • Carcinoid Tumor / diagnosis
  • Carcinoid Tumor / mortality
  • Carcinoid Tumor / pathology
  • Female
  • Humans
  • Ki-67 Antigen / analysis*
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology*
  • Male
  • Medical Oncology / methods*
  • Middle Aged
  • Neoplasm Grading / methods*
  • Neuroendocrine Tumors / classification
  • Neuroendocrine Tumors / diagnosis
  • Neuroendocrine Tumors / mortality
  • Neuroendocrine Tumors / pathology*
  • Practice Patterns, Physicians'
  • Prognosis
  • Surveys and Questionnaires

Substances

  • Biomarkers, Tumor
  • Ki-67 Antigen