Pleural mesothelioma from fluoro-edenite exposure: PACAP and PAC1 receptor. A preliminary report

Our plain-English summary of Pleural mesothelioma from fluoro-edenite exposure: PACAP and PAC1 receptor. A preliminary report, by C. Lombardo, G. Maugeri, A.G. D'Amico, et al (European Journal of Histochemistry, 2024).

The study

• Authors: C. Lombardo, G. Maugeri, A.G. D'Amico, G. Broggi, R. Caltabiano, V. Filetti, S. Matera, V. D'Agata, C. Loreto
• Journal: European Journal of Histochemistry
• Published: 2024;68(2)
• Read it: PubMed · Publisher · Free full text

Abstract

Pleural mesothelioma is a devastating malignancy primarily associated with asbestos exposure. However, emerging evidence suggests that exposure to fluoro-edenite fibers, a naturally occurring mineral fiber, can also lead to the development of pleural mesothelioma. In this study, based on the hypothesis that pituitary adenylate cyclase-activating polypeptide (PACAP) and PACAP-preferring receptor (PAC1R) expressions could be dysregulated in pleural mesothelioma samples and that they could potentially act as diagnostic or prognostic biomarkers, we aimed to investigate the immunohistochemical expression of PACAP and PAC1R in pleural biopsies from patients with pleural mesothelioma exposed to fluoro-edenite fibers. A total of 12 patients were included in this study, and their biopsies were processed for immunohistochemical analysis to evaluate the expression of PACAP and its receptor. The study revealed a correlation between the overexpression of PACAP and PAC1R and shorter overall survival in patients with malignant mesothelioma. These findings suggest that PACAP and PAC1R expression levels could serve as potential prognostic biomarkers for malignant mesothelioma. Furthermore, the immunohistochemical analysis of PACAP and PAC1R may provide valuable information for clinicians to guide therapeutic decisions and identify patients with poorer prognosis.

In plain English

This brief report from the University of Catania, Italy, was a retrospective laboratory study of stored pleural tissue from 12 patients with malignant pleural mesothelioma. All had been exposed to fluoro-edenite, a fibrous amphibole mineral. The article says ten lived in Biancavilla or nearby contaminated areas, without saying where the other two lived. Six tumors were epithelioid, three biphasic and three sarcomatoid. They were compared with pleural tissue from eight people without cancer living outside Biancavilla. The authors stained the tissue for PACAP, a signaling molecule, and its receptor, PAC1R. PAC1R was highly expressed in all tumors. PACAP was high in all six epithelioid tumors, low in biphasic tumors and absent in sarcomatoid tumors. Control tissue also stained for both. The stained area and the staining intensity were both higher in tumors than in controls; for PACAP stained area, p was 0.0068. The authors concluded that PACAP could be a useful marker for epithelioid and biphasic tumors, and said larger studies were needed. The abstract reports a link with shorter survival, but the article's results describe no survival analysis.

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, non-interventional immunohistochemical study of archived tissue, published as a brief report and described as preliminary
• Who was studied: Archived pleural biopsy samples from 12 patients with malignant pleural mesothelioma (7 men, 5 women, aged 50 to 93, average 67) from the biobank of the Section of Anatomic Pathology, University of Catania, Italy. There were 6 epithelioid, 3 biphasic and 3 sarcomatoid tumors. The control group was 8 people without cancer who did not live in Biancavilla (aged 15 to 76, average 44); their pleural tissue was taken during surgery for pulmonary emphysema or pleurisy. Collection dates are not given.
• Exposure: Exposure to fluoro-edenite fibers (a fibrous amphibole) is reported for all 12 patients. The article says ten of the patients were residents of Biancavilla or neighboring areas affected by environmental contamination with silicate fibers. It does not say where the other two lived, and it gives no exposure levels.
• Main results:
  • PAC1R was highly expressed in all 12 mesothelioma cases, whatever the tumor subtype.
  • PACAP expression was high in all 6 epithelioid cases (6/12, 50%), low in biphasic cases and absent in sarcomatoid cases. The table shows 0 stained area for all three sarcomatoid cases.
  • All control (unaffected mesothelium) samples showed staining for both PAC1R and PACAP.
  • The percentage of tissue area stained was higher in the mesothelioma samples than in the controls, for PACAP (p=0.0068) and for PAC1R (p less than 0.0001).
  • Staining intensity was higher in the mesothelioma samples than in the controls, for PACAP (p=0.0049) and for PAC1R (p=0.0005).
• The authors' conclusion: The authors concluded that they had identified PACAP as an innovative and useful marker for the epithelioid and biphasic subtypes of pleural mesothelioma, and that it could help tell subtypes apart.
• Limitations the authors state:
  • The authors stated that further studies on larger series are needed to validate the finding of reduced PACAP in the sarcomatoid subtype, and that they hope to confirm the data with more cases.

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, fluoro-edenite, Asbestos Exposure, Mineral Fiber, Biomarker, Overall Survival, Malignant Mesothelioma, Prognosis.

Related studies

• Immunohistochemical Expression of Serine and Arginine-Rich Splicing Factor 1 (SRSF1) in Fluoro-Edenite-Induced Malignant Mesothelioma: A Preliminary Study — G. Broggi, G. Angelico, et al. (2021)
• Immunohistochemical Expression of Aquaporin-1 in Fluoro-Edenite-Induced Malignant Mesothelioma: A Preliminary Report — G. Angelico, R. Caltabiano, et al. (2018)
• Fibulin-3 immunoexpression in malignant mesothelioma due to fluoro-edenite: a preliminary report — R. Caltabiano, C. Loreto, et al. (2018)
• Angiogenesis correlates with macrophage and mast cell infiltration in lung tissue of animals exposed to fluoro-edenite fibers — G. Musumeci, C. Loreto, et al. (2016)
• Immunohistochemical expression of retinoblastoma and phospho-retinoblastoma protein in sheep lung exposed to fluoro-edenite fibers — G. Musumeci, C. Loreto, et al. (2010)
• Early effects of fluoro-edenite: correlation between IL-18 serum levels and pleural and parenchymal abnormalities — C. Ledda, C. Loreto, et al. (2016)

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