The Role of Ki-67 and Pre-cytoreduction Parameters in Selecting Diffuse Malignant Peritoneal Mesothelioma (DMPM) Patients for Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC)

Ann Surg Oncol. 2016 May;23(5):1468-73. doi: 10.1245/s10434-015-4962-9. Epub 2015 Nov 16.


Background: We conducted a prognostic analysis of preoperative parameters and Ki-67 determination to develop selection criteria for cytoreductive surgery (CRS) and HIPEC in patients with diffuse malignant peritoneal mesothelioma (DMPM).

Methods: DMPM patients treated with CRS and HIPEC at NCI of Milan participated in this study. Multivariate analysis was conducted using Cox proportional hazard model and conditional inference tree method to select independent predictors of overall survival (OS) from the followings pre-cytoreduction parameters: age, sex, ECOG performance status, Charlson comorbidity index, previous systemic chemotherapy, CA-125, histological subtype (epithelioid vs. biphasic/sarcomatoid), Ki-67 (determined with immunohistochemistry), and peritoneal cancer index (PCI).

Results: A total of 117 patients (male/female: 67/50) with median age of 60.5 (range 22-75) years were included. Eighty-three patients had ECOG performance status = 0, median Charlson comorbidity index was 4 (range 2-9), and 102 cases had epithelioid subtype. Median Ki-67 was 5 % (range 1-60). Ninety-four (80.3 %) cases were optimally cytoreduced. The Cox analysis identified Ki-67, PCI, and histological subtype as independent prognosticators of OS. Conditional inference tree method identified three prognostic subsets: (I) Ki-67 ≤ 9 %; (II) Ki-67 > 9 % and PCI ≤ 17; and (III) Ki-67 > 9 % and PCI > 17. The median OS for subsets I, II, and III were, 86.6, 63.2, and 10.3 months, respectively.

Conclusions: Ki-67 is a powerful prognosticator that allows, along with PCI, and histological subtype, a good prediction of OS in patients with DMPM. Patients with Ki-67 > 9 % and PCI > 17 are unlikely to benefit from the procedure and should be considered for other treatment protocols.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / metabolism
  • Chemotherapy, Cancer, Regional Perfusion*
  • Combined Modality Therapy
  • Cytoreduction Surgical Procedures*
  • Female
  • Follow-Up Studies
  • Humans
  • Hyperthermia, Induced*
  • Immunoenzyme Techniques
  • Ki-67 Antigen / metabolism*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Lung Neoplasms / therapy
  • Male
  • Mesothelioma / metabolism
  • Mesothelioma / pathology*
  • Mesothelioma / therapy
  • Mesothelioma, Malignant
  • Middle Aged
  • Neoplasm Staging
  • Peritoneal Neoplasms / metabolism
  • Peritoneal Neoplasms / secondary*
  • Peritoneal Neoplasms / therapy
  • Prognosis
  • Proportional Hazards Models
  • Prospective Studies
  • Retrospective Studies
  • Risk Assessment
  • Survival Rate
  • Young Adult


  • Biomarkers, Tumor
  • Ki-67 Antigen