Ki67 index is an independent prognostic factor in epithelioid but not in non-epithelioid malignant pleural mesothelioma: a multicenter study

Br J Cancer. 2015 Mar 3;112(5):783-92. doi: 10.1038/bjc.2015.9. Epub 2015 Jan 29.

Abstract

Background: Estimating the prognosis in malignant pleural mesothelioma (MPM) remains challenging. Thus, the prognostic relevance of Ki67 was studied in MPM.

Methods: Ki67 index was determined in a test cohort of 187 cases from three centres. The percentage of Ki67-positive tumour cells was correlated with clinical variables and overall survival (OS). The prognostic power of Ki67 index was compared with other prognostic factors and re-evaluated in an independent cohort (n=98).

Results: Patients with Ki67 higher than median (>15%) had significantly (P<0.001) shorter median OS (7.5 months) than those with low Ki67 (19.1 months). After multivariate survival analyses, Ki67 proved to be-beside histology and treatment-an independent prognostic marker in MPM (hazard ratio (HR): 2.1, P<0.001). Interestingly, Ki67 was prognostic exclusively in epithelioid (P<0.001) but not in non-epithelioid subtype. Furthermore, Ki67 index was significantly lower in post-chemotherapy samples when compared with chemo-naive cases. The prognostic power was comparable to other recently published prognostic factors (CRP, fibrinogen, neutrophil-to-leukocyte ratio (NLR) and nuclear grading score) and was recapitulated in the validation cohort (P=0.048).

Conclusion: This multicentre study demonstrates that Ki67 is an independent and reproducible prognostic factor in epithelioid but not in non-epithelioid MPM and suggests that induction chemotherapy decreases the proliferative capacity of MPM.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Epithelioid Cells / metabolism
  • Epithelioid Cells / pathology*
  • Female
  • Humans
  • Ki-67 Antigen / metabolism*
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / mortality*
  • Lung Neoplasms / pathology
  • Male
  • Mesothelioma / drug therapy
  • Mesothelioma / metabolism
  • Mesothelioma / mortality*
  • Mesothelioma / pathology
  • Mesothelioma, Malignant
  • Middle Aged
  • Pleural Neoplasms / drug therapy
  • Pleural Neoplasms / metabolism
  • Pleural Neoplasms / mortality*
  • Pleural Neoplasms / pathology
  • Survival Analysis
  • Treatment Outcome

Substances

  • Ki-67 Antigen