Prognostic Value of Ki67 Percentage, WT-1 Expression and p16/CDKN2A Deletion in Diffuse Malignant Peritoneal Mesothelioma: A Single-Centre Cohort Study

Our plain-English summary of Prognostic Value of Ki67 Percentage, WT-1 Expression and p16/CDKN2A Deletion in Diffuse Malignant Peritoneal Mesothelioma: A Single-Centre Cohort Study, by F. Pezzuto, G. Serio, F. Fortarezza, et al (Diagnostics, 2020).

The study

• Authors: F. Pezzuto, G. Serio, F. Fortarezza, A. Scattone, C. Caporusso, A. Punzi, D. Cavone, A. Pennella, A. Marzullo, L. Vimercati
• Journal: Diagnostics
• Published: 2020;10(6)
• Cited by: 22 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Diffuse malignant peritoneal mesothelioma (DMPM) is a rare malignant neoplasm with a poor survival. Although some advances in knowledge have been obtained for the pleural form, much less is known about DMPM. Advantages in terms of prognosis are still limited and strong efforts need to be made. The aim of our study was to correlate several histological and molecular factors with survival in a large cohort of 45 DMPMs. We evaluated histotype, nuclear grade, mitotic count, necrosis, inflammation, desmoplastic reaction, Ki67 percentage, WT-1 expression, p16 protein by immunohistochemistry and CDKN2A deletion by FISH. Our results showed that epithelioid histotype, nuclear grade 2, mitotic count ≤5 x mm2, absence of desmoplasia and p16/CDKN2A deletion, low Ki67 value, and high WT-1 expression were correlated with the most prolonged survival (p = 0.0001). Moreover, p16 loss in immunohistochemistry reflected CDKN2A deletion detected with FISH, and both were correlated with the worst survival (p = 0.0001). At multivariate analysis, Ki67 value, WT-1 expression and p16/CDKN2A deletion emerged as independent prognostic factors (p = 0.01, p = 0.0001 and p = 0.01, respectively). These parameters are easy to analyse at the time of DMPM diagnosis and may support better patient stratification, prediction of treatment effectiveness and therapeutic optimization.

In plain English

This study looked back at 45 cases of diffuse malignant peritoneal mesothelioma (mesothelioma of the abdominal lining) diagnosed one after another at the University of Bari, Italy, between March 1990 and May 2012. There were 35 men and 10 women, and asbestos exposure was known in 28 of the 45. The authors examined tumour tissue for its cell type and for four laboratory markers: Ki67, a sign of cell growth; the WT-1 protein; the p16 protein; and loss of the CDKN2A gene. They then compared these features with survival. Mean survival was 15.3 months. Epithelioid tumours had longer mean survival (19.7 months) than biphasic (4.8) or sarcomatoid (2.7) tumours. Low Ki67, high WT-1 and absent or partial CDKN2A loss went with better survival. Ki67, WT-1 and p16/CDKN2A loss were independent predictors in a combined analysis. No correlation was found between CDKN2A loss and asbestos exposure. The authors concluded these tests could help identify patients at highest risk of short survival. They noted the study was retrospective, came from one centre, covered a long period, and could not evaluate asbestos exposure data.

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: Single-centre retrospective cohort study of tumour samples, relating tissue and molecular features to survival (Kaplan-Meier and Cox regression analysis)
• Who was studied: 45 patients with diffuse malignant peritoneal mesothelioma diagnosed consecutively at the Pathology section of the University of Bari, Italy, March 1990 to May 2012: 35 male and 10 female, mean age 63.7 years (plus or minus 11.5)
• Exposure: The study was about tumour features, not asbestos dose. Asbestos exposure (occupational and/or environmental) was collected by questionnaire or family interview and was known in 28 of the 45 patients (62.2%). No fiber types were reported.
• Main results:
  • Mean survival for the whole group was 15.3 months (plus or minus 2.6).
  • Mean survival differed by tumour type: epithelioid 19.7 months, biphasic 4.8 months, sarcomatoid 2.7 months (p = 0.0001).
  • Patients with Ki67 of 25% or less and those with WT-1 above 15% had better survival than their counterparts (p = 0.0001 each).
  • In the multivariate analysis, Ki67 percentage, WT-1 expression and p16/CDKN2A deletion were independent predictors of survival (p = 0.01, p = 0.001, p = 0.017, respectively).
  • Homozygous (complete) CDKN2A deletion was found in 23 of the 45 cases (51.1%). All 23 patients with negative p16 staining also had a homozygous deletion on FISH testing.
  • CDKN2A deletion was more frequent in females (p = 0.005), as well as in biphasic/sarcomatoid tumours and in tumours with high grade, high mitotic count, high proliferative index and low WT-1.
  • No correlation was found between CDKN2A deletion and asbestos exposure.
  • Mean survival was comparable for patients diagnosed 1990 to 2003 and those diagnosed 2004 to 2012 (12.2 vs. 12.4 months).
• The authors' conclusion: The authors concluded that Ki67, WT-1 and p16 immunohistochemistry, combined with FISH analysis, could be useful in identifying patients at highest risk of short survival and in better grouping patients with diffuse malignant peritoneal mesothelioma by expected outcome.
• Limitations the authors state:
  • The study was single-centre and retrospective, and specimens were collected over a long time period.
  • Some important factors could not be evaluated, including data on asbestos exposure and specific chemotherapy schemes.

Topics

Medical terms in this study, explained in our Lexicon: Wilms Tumor 1 (WT-1), CDKN2A, Peritoneal Mesothelioma, Cohort Study, Neoplasm, Prognosis, Nuclear Grade, Mitotic Count.

Related studies

• Evaluation of prognostic histological parameters proposed for pleural mesothelioma in diffuse malignant peritoneal mesothelioma. A short report — F. Pezzuto, L. Vimercati, et al. (2021)
• CDKN2A and MTAP deletions in peritoneal mesotheliomas are correlated with loss of p16 protein expression and poor survival — A.M. Krasinskas, D.L. Bartlett, et al. (2010)
• High Wilms' tumour gene (WT1) expression and low mitotic count are independent predictors of survival in diffuse peritoneal mesothelioma — A. Scattone, G. Serio, et al. (2012)
• Homozygous deletion of CDKN2A in malignant mesothelioma: Diagnostic utility, patient characteristics and survival in a UK mesothelioma centre — K. Marshall, S. Jackson, et al. (2020)
• The value of BRCA-1-associated protein 1 expression and cyclin-dependent kinase inhibitor 2A deletion to distinguish peritoneal malignant mesothelioma from peritoneal location of carcinoma in effusion cytology specimens — W. Althakfi, S. Gazzo, et al. (2020)
• Prognostic associations of PD-L1 expression and BAP1 loss in pleural mesothelioma: a retrospective single-center cohort from Colombia — R. Brugés, C. Carvajal, et al. (2026)

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