Prognostic significance of Ki67 expression in malignant peritoneal mesothelioma

Our plain-English summary of Prognostic significance of Ki67 expression in malignant peritoneal mesothelioma, by K. Pillai, M.H. Pourgholami, T.C. Chua, et al (American Journal of Clinical Oncology, 2015).

The study

• Authors: K. Pillai, M.H. Pourgholami, T.C. Chua, D.L. Morris
• Journal: American Journal of Clinical Oncology
• Published: 2015;38(4):388-94
• Cited by: 22 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objectives: Although Ki67 measurement by immunohistochemistry has been widely used as a prognostic index in cancers, it has not been reported in malignant peritoneal mesothelioma (MPM). Hence, this study examines the prognostic significance of Ki67 in MPM.

Methods: Specimens from 42 MPM patients were screened for Ki67 expression using immunohistochemistry. Ki67 expression was classified into 2 groups on the basis of expression (<25%=low; ≥25%=high) using standard methods. Using Kaplan-Meier survival analysis, the significance of Ki67 was assessed in different clinicopathologic categories.

Results: High expression of Ki67 (≥25% by immunohistochemical evaluation) was correlated with poor survival in the overall group (P=0.001); male sex (P=0.001); female sex (P=0.001); epithelioid tumors (P=0.001): male epithelioid (P=0.001), female epithelioid (P=0.003); peritoneal cancer index (PCI): PCI<20 (P=0.001), PCI≥20 (P=0.002); and age at diagnosis (AAD): AAD<60 years (P=0.001), AAD≥60 years (P=0.004). Independent of Ki67, male sex (P=0.007), sarcomatoid histology (P=0.001), PCI≥20 (P=0.013), and AAD≥60 years (P=0.004) correlated with poor survival. Multivariate analysis showed that only AAD≥60 years (P=0.049) and high Ki67 expression for all tumors (P=0.031), male sex (P=0.038), female sex (P=0.021), epithelioid tumors (P=0.044), and AAD<60 years (P=0.029) were statistically significant.

Conclusions: Ki67 expression affects prognosis in MPM patients and helps to predict survival within the various clinicopathologic categories.

In plain English

This was a retrospective study from St George Hospital, Kogarah, Australia. It looked at stored tumor samples from 42 patients with malignant peritoneal mesothelioma (20 men, 22 women). All had cytoreductive surgery and heated intraperitoneal chemotherapy (HIPEC) between 1999 and 2012. The study did not examine asbestos exposure. The authors stained the tumors for Ki67, a protein found in dividing cells, calling 25% or more stained cells "high." Of the 42 patients, 27 had low and 15 had high Ki67. Overall, all low-Ki67 patients were alive at 5 years; none of the high-Ki67 patients were. In the multivariate analysis, high Ki67 was associated with poorer survival overall (hazard ratio 4.78, 95% CI 1.9 to 17.6). It was also linked to poorer survival in men, women, epithelial tumors and patients diagnosed before age 60. Age 60 or older at diagnosis was also associated with poorer survival in that analysis (hazard ratio 3.3, 95% CI 1.4 to 16.4). In sarcomatoid tumors, the Ki67 result was not statistically significant. The authors concluded that Ki67 is a prognostic factor, noting their small sample limited the statistics.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective study of archived tumor specimens, with survival analysis (Kaplan-Meier, log-rank and Cox regression)
• Who was studied: 42 patients with malignant peritoneal mesothelioma (20 male, 22 female; median age 57, range 23 to 69) treated with cytoreductive surgery and HIPEC at St George Hospital, Kogarah, NSW, Australia, between January 1999 and February 2012
• Exposure: Not an asbestos exposure study. The factor studied was Ki67 expression in tumor tissue, measured by immunohistochemistry (MIB-1 antibody). Below 25% of tumor cells stained was classed as low; 25% or more was classed as high. Asbestos is mentioned only in the discussion, as background on latency.
• Main results:
  • Of the 42 patients, 27 (64%) had low Ki67 and 15 (36%) had high Ki67
  • In the overall patient group, all low-Ki67 patients were alive at 5 years; none of the high-Ki67 patients were
  • In univariate analysis, high Ki67 was associated with poor survival in almost all clinicopathologic categories examined
  • In multivariate analysis, high versus low Ki67 for all tumors: hazard ratio 4.78 (95% CI 1.9 to 17.6), P = 0.031
  • In multivariate analysis, high versus low Ki67 in male patients: HR 4.3 (95% CI 1.3 to 19.8), P = 0.038. In female patients: HR 2.9 (95% CI 1.2 to 16.4), P = 0.021
  • In multivariate analysis, high versus low Ki67 in epithelial tumors: HR 6.6 (95% CI 3.1 to 59.3), P = 0.044. In patients diagnosed before age 60: HR 3.8 (95% CI 1.44 to 16.9), P = 0.029
  • Apart from Ki67, only age at diagnosis of 60 years or older was a significant independent poor prognostic factor in multivariate analysis: HR 3.3 (95% CI 1.4 to 16.4), P = 0.049
  • In multivariate analysis, sarcomatoid versus epithelioid histology was not statistically significant (HR 3.3, 95% CI 0.1 to 10, P = 0.117)
  • In sarcomatoid tumors, high Ki67 had a relative risk of 14.1, but this was not statistically significant; the authors attributed this to the small number of tumors
• The authors' conclusion: The authors concluded that Ki67 is an 'important prognostic factor' in malignant peritoneal mesothelioma. They wrote that routine monitoring of Ki67 may help estimate a patient's prognosis more precisely.
• Limitations the authors state:
  • Because the disease is rare, the sample was small, with inherent statistical compromise; the authors suggested a multi-institutional study
  • The authors had no data on patients' hormone levels to support their hypothesis about sex differences

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma, Peritoneal mesothelioma.

Medical terms in this study, explained in our Lexicon: Peritoneal Mesothelioma, Immunohistochemistry, Epithelioid, Peritoneal Cancer Index (PCI), Sarcomatoid, Histology, Multivariate Analysis, Prognosis.

Related studies

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• Impact of tumor angiogenesis in peritoneal mesothelioma after radical cytoreduction and hyperthermic intraperitoneal chemotherapy — T.C. Chua, P. Yao, et al. (2010)
• Immunohistochemical evaluation of two antibodies against PD-L1 and prognostic significance of PD-L1 expression in epithelioid peritoneal malignant mesothelioma: A RENAPE study — S. Valmary-Degano, P. Colpart, et al. (2017)
• Does the expression of BCL2 have prognostic significance in malignant peritoneal mesothelioma? — K. Pillai, M.H. Pourgholami, et al. (2013)
• The results of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in 1200 patients with peritoneal malignancy — B. Moran, T. Cecil, et al. (2015)
• Iterative procedures combining cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for isolated peritoneal recurrence — M. Vaira, M. Robella, et al. (2014)

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