High Wilms' tumour gene (WT1) expression and low mitotic count are independent predictors of survival in diffuse peritoneal mesothelioma

Our plain-English summary of High Wilms' tumour gene (WT1) expression and low mitotic count are independent predictors of survival in diffuse peritoneal mesothelioma, by A. Scattone, G. Serio, A. Marzullo, et al (Histopathology, 2012).

The study

• Authors: A. Scattone, G. Serio, A. Marzullo, P. Nazzaro, F. Corsi, M.P. Cocca, M. Mattoni, A. Punzi, M. Gentile, A.L. Buonadonna, A. Pennella
• Journal: Histopathology
• Published: 2012;60(3):472-81
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Aims: To evaluate the use of the Wilms' tumour gene (WT1) marker and histomorphological parameters as indicators of prognosis in malignant peritoneal mesothelioma (MPM).

Methods And Results: Histological samples of 31 MPM were stained immunohistochemically for the WT1 protein. The results were quantified by recording the number of stained nuclei, and then correlated with patient survival. Statistical correlation was evaluated for tumour histotype, mitotic count (MC), nuclear grade (NG), necrosis, lymphoid response (grade of inflammation) and desmoplasia with regard to survival. High-grade histology (solid epithelioid, pure sarcomatoid or biphasic tumours), high NG, MC more than five per 10 per high-power field (HPF), necrosis and desmoplasia were associated with a significantly worse prognosis. Patients with MPM with low WT1 expression (≤25% of positive cells) survived for a significantly shorter time compared to those with high WT1 expression (>25% of positive cells) (P = 0.0001). The 50% survival time of subjects with low WT1 expression was 2.9 months [95% confidence interval (CI): 2.05-3.71] versus 31.5 months (95% CI: 20.4-42.5) for those with high WT1 expression. On multivariate analysis, WT1 and MC were found to be associated independently with survival (P = 0.002; P = 0.005, respectively).

Conclusions: Our study suggests that low WT1 expression and high MC may be indicative of an unfavourable prognosis in patients with advanced malignant peritoneal mesothelioma.

© 2012 Blackwell Publishing Limited.

In plain English

This study examined biopsies from 31 patients with diffuse malignant peritoneal mesothelioma diagnosed between March 1990 and February 2009 at Bari University Hospital, Italy. Fifteen (48.4%) had a history of occupational or domestic asbestos exposure; no fiber types are named. None had cytoreductive surgery, and all received only chemotherapy. Tumours were stained for the WT1 protein, scored for features, and compared with survival. Overall median survival was 5 months. Mean survival was 2.9 months (95% CI 2.05 to 3.71) for the 21 patients whose tumours had 25% or fewer WT1-positive cells, versus 31.5 months (95% CI 20.4 to 42.5) for the 10 with more than 25% (P = 0.0001). Patients with five or fewer mitoses per 10 high-power fields (13 cases) had a mean survival of 26 months (95% CI 13.6 to 38.3), versus 5.7 months (95% CI 2.4 to 9) for the other 18 (P = 0.002). Epithelioid tumour type and lower nuclear grade were also linked to longer survival. In multivariate analysis, WT1 and mitotic count were independently associated with survival. The authors concluded these may be considered major prognostic parameters.

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 pathology study of patient biopsies, with survival analysis (Kaplan–Meier, log-rank test, Cox regression)
• Who was studied: 31 patients (25 males, 6 females, aged 36 to 80) with diffuse malignant peritoneal mesothelioma, diagnosed between March 1990 and February 2009 at the Department of Pathology, Bari University Hospital, Italy. None had cytoreduction, and all received only adjuvant chemotherapy.
• Exposure: The study was about tumour markers, not about exposure. It reports only that 15 patients (48.4%) had a history of occupational or domestic asbestos exposure. No fiber types or doses are given.
• Main results:
  • For all 31 patients, survival ranged from 1 to 60 months, with a median survival time of 5 months.
  • Low WT1 group (25% or fewer positive cells, 21 cases): mean survival 2.9 months (95% CI 2.05 to 3.71). High WT1 group (more than 25%, 10 cases): mean survival 31.5 months (95% CI 20.4 to 42.5). P = 0.0001.
  • Mitotic count of five or fewer per 10 high-power fields (13 cases, 41.9%): mean survival 26 months (95% CI 13.6 to 38.3). Higher mitotic count (18 cases): mean survival 5.7 months (95% CI 2.4 to 9). P = 0.002.
  • Mean survival by histological type: epithelioid (20 cases) 20.8 months, biphasic (7 cases) 4.9 months, sarcomatoid (4 cases) 2.7 months. The differences were statistically significant (P = 0.006).
  • Nuclear grade 2 (9 cases): mean survival 37 months. Nuclear grade 3 (22 cases): mean survival 4.3 months. P = 0.0001.
  • Among epithelioid tumours, tubulopapillary or microcystic variants (9 cases) had a mean survival of 38.1 months, versus 6.6 months for solid epithelioid tumours (11 cases). P = 0.0001.
  • In univariate analysis, necrosis and desmoplasia were each associated with a worse prognosis (P = 0.05 and P = 0.006).
  • In multivariate Cox regression, which also included age, sex, histology, necrosis, lymphoid reaction and desmoplasia, WT1 and mitotic count were independent predictive variables (P = 0.002 and P = 0.005).
• The authors' conclusion: The authors concluded that WT1 expression and mitotic count are independent predictors of survival and may be considered major prognostic parameters in diffuse malignant peritoneal mesothelioma.

Topics

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

Medical terms in this study, explained in our Lexicon: Mitotic Count, Peritoneal Mesothelioma, Prognosis, Nuclear Grade, Necrosis, Inflammation, Histology, Epithelioid.

Related studies

• Expression of Wilms' tumor gene (WT1) is associated with survival in malignant pleural mesothelioma — S. Cedrés, M.A. Montero, et al. (2014)
• Expression of the Wilms' tumor gene WT1 in human malignant mesothelioma cell lines and relationship to platelet-derived growth factor A and insulin-like growth factor 2 expression — A.W. Langerak, K.A. Williamson, et al. (1995)
• Preoperative Circulating Tumor DNA in Patients with Peritoneal Carcinomatosis is an Independent Predictor of Progression-Free Survival — J.M. Baumgartner, V.M. Raymond, et al. (2018)
• Combined grade and nuclear grade are prognosis predictors of epithelioid malignant peritoneal mesothelioma: a multi-institutional retrospective study — N. Benzerdjeb, P. Dartigues, et al. (2021)
• Expression of genes coding for proteoglycans and Wilms' tumour susceptibility gene 1 (WT1) by variously differentiated benign human mesothelial cells — M. Gulyás, K. Dobra, et al. (1999)
• Survivin expression as an independent predictor of overall survival in malignant peritoneal mesothelioma — G. Zhang, D.L. Yang, et al. (2020)

Browse more research in Histopathology, or return to medical research.