BAP1, Wilms' tumor 1, and calretinin in predicting survival and response to first-line chemotherapy in patients with pleural mesothelioma

Our plain-English summary of BAP1, Wilms' tumor 1, and calretinin in predicting survival and response to first-line chemotherapy in patients with pleural mesothelioma, by T.H. Yuce, G. Ak, S. Metintas, et al (Journal of Cancer Research and Clinical Oncology, 2024).

The study

• Authors: T.H. Yuce, G. Ak, S. Metintas, E. Dundar, O.D. Roe, V. Panou, M. Metintas
• Journal: Journal of Cancer Research and Clinical Oncology
• Published: 2024;150(2):38
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Purpose: There are currently no methods to predict response to chemotherapy in pleural mesothelioma (PM). The aim of this study is to investigate the predictive and prognostic role of BAP1, WT1 and calretinin expression and their combinations in pre-treatment tumor samples by immunohistochemical (IHC) staining.

Methods: The study included consecutive PM patients treated with chemotherapy alone at a University hospital between 2009 and 2020. BAP1 analyses were performed on formalin-fixed, paraffin-embedded tumor tissue samples of the patients, while WT1 and calretinin information were obtained from the histopathological diagnosis records.

Results: Of the total 107 patients included, 64% had loss of BAP1 expression, whereas 77% had WT1 and 86% had calretinin expression. Patients with the presence of BAP1 expression, one or both of the other two markers, or loss of expression of all three markers (unfavorable status) were more likely to not respond to chemotherapy than those with the presence of all three markers or loss of BAP1 expression and expression of one or two other markers (favorable status) (p = 0.001). Median survival time of patients with favorable and unfavorable status was 15 ± 1.7 and 8.0 ± 2.4 months, respectively (p = 0.027). After adjustment for histopathology and stage, loss of BAP1 (HR = 0.54, 95%CI 0.35-0.83), WT1 (1.75, 1.06-2.90), calretinin (2.09, 1.14-3.84) expression and favourable panel (0.50, 0.27-0.92) was associated with prognosis.

Conclusions: The IHC biomarkers BAP1, WT1, and calretinin, used in the routine diagnosis of PM and their combinations, are the first biomarkers associated with response to chemotherapy and may be a useful tool to select patients for first-line platinum pemetrexed treatment in PM patients. Validation in a large cohort is ongoing.

© 2024. The Author(s).

In plain English

This study, from a university hospital in Eskisehir, Turkey, looked at 107 patients with pleural mesothelioma treated between 2009 and 2020 with first-line pemetrexed plus cisplatin or carboplatin chemotherapy. Some patients also received radiotherapy for pain control. The authors reported that all patients had been exposed to environmental asbestos in rural areas. The researchers stained stored tumor tissue for BAP1 and took WT1 and calretinin results from the original diagnostic records. BAP1 was lost in 64.5% of patients. Among 103 patients with all three results, the authors defined unfavorable and favorable marker patterns. Eleven of 13 unfavorable-pattern patients had disease progression, while 24 of 90 favorable-pattern patients responded to chemotherapy (p = 0.001). Median survival was 15 months with the favorable pattern versus 8.0 months with the unfavorable pattern. After adjusting for tumor type and stage, BAP1 loss and the favorable pattern were associated with a lower risk of death, and loss of WT1 or calretinin with a higher risk. The authors concluded the markers may help predict response and survival, pending validation in larger studies. They noted the single-center design and the few sarcomatoid cases.

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-center cohort study. The researchers stained stored tumor tissue for BAP1. WT1 and calretinin results came from the original pathology diagnosis records.
• Who was studied: Patients aged 25 to 85 with pleural mesothelioma, treated with first-line pemetrexed-platinum chemotherapy at Eskisehir Osmangazi University, Turkey, 2009 to 2020. Patients who also received palliative radiotherapy for pain control were included. There were 68 men and 39 women. Tumor types were 74 epithelioid, 25 biphasic and 8 sarcomatoid.
• Exposure: The study examined tumor markers (BAP1, WT1, calretinin) and response to pemetrexed-cisplatin or pemetrexed-carboplatin. The authors state all patients had environmental asbestos exposure in rural areas. No fiber type or dose is given.
• Main results:
  • 107 patients were included, and all three stains could be evaluated in 103 of them.
  • Loss of BAP1 expression in tumor tissue was found in 64.5% of patients (69 of 107 in Table 2).
  • Unfavorable marker pattern: 11 of 13 patients (84.6%) had progressive disease, and the other 2 had stable disease.
  • Favorable marker pattern: of 90 patients, 24 (26.7%) had an objective response, 33 (36.7%) had stable disease and 33 (36.7%) had progressive disease. Unfavorable-pattern patients were more likely not to respond than favorable-pattern patients (p = 0.001).
  • After excluding sarcomatoid patients, response in the remaining 97 patients was still worse in the unfavorable group than in the favorable group (p = 0.046).
  • Taken one at a time, WT1 and calretinin expression were higher in patients with an objective response (p = 0.054 and p = 0.003). The study's significance threshold was p of 0.05 or less. BAP1 loss did not differ significantly between response groups.
  • Median survival was 15 ± 1.7 months in the favorable-pattern group and 8.0 ± 2.4 months in the unfavorable-pattern group (p = 0.027).
  • Without adjustment, survival was longer in patients with BAP1 loss, but the difference was not statistically significant (p = 0.082). The unadjusted hazard ratio was 0.71 (0.47 to 1.06), p = 0.095.
  • After adjustment for tumor type and stage, hazard ratios for death were 0.54 (95% CI 0.35 to 0.83) for loss versus retention of BAP1, and 1.75 (1.06 to 2.90) for loss versus retention of WT1.
  • After adjustment for tumor type and stage, hazard ratios for death were 2.09 (1.14 to 3.84) for loss versus retention of calretinin, and 0.50 (0.27 to 0.92) for the favorable versus the unfavorable pattern.
  • Patients with loss of all three markers did not respond (5 of 5). All patients with retained BAP1 but loss of both WT1 and calretinin progressed (5 of 5).
• The authors' conclusion: The authors concluded that BAP1, WT1 and calretinin, simple stains used in routine pathology, may be useful in determining response and prognosis after platinum-pemetrexed chemotherapy. They said the results remain to be validated in larger studies.
• Limitations the authors state:
  • The study was single-center, with a limited number of patients with the sarcomatoid subtype.
  • WT1 and calretinin were also highly expressed in patients whose disease progressed, which the authors say hampers clinical use of these markers alone.
  • The results need validation in larger studies.

Topics

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

Medical terms in this study, explained in our Lexicon: BAP1, Calretinin, Chemotherapy, Pleural Mesothelioma, Median Overall Survival, Histopathology, Prognosis, Biomarker.

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