Mesothelioma and Colorectal Cancer: Report of Four Cases with Synchronous and Metachronous Presentation

Our plain-English summary of Mesothelioma and Colorectal Cancer: Report of Four Cases with Synchronous and Metachronous Presentation, by G. Serio, F. Pezzuto, F. Fortarezza, et al (International Journal of Molecular Sciences, 2022).

The study

• Authors: G. Serio, F. Pezzuto, F. Fortarezza, A. Marzullo, M.C. Delfino, A. d'Amati, D.E. Romano, S. Maniglio, C. Caporusso, T. Lettini, D. Cavone, L. Vimercati
• Journal: International Journal of Molecular Sciences
• Published: 2022;23(5)
• Type of article: Case report
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

There is evidence that asbestos could play a role in the carcinogenesis of digestive cancers. The presence of asbestos fibres in histological samples from gastric, biliary, colon cancers has been reported, but the mechanism is still controversial. It has been hypothesised that asbestos reaches these sites, especially through contaminated water; however, some experimental studies have shown that the inhaled fibres are mobile, so they can migrate to many organs, directly or via blood and lymph flow. We report four unusual cases of colorectal cancers in patients with a long history of asbestos exposure who also developed synchronous or metachronous mesothelioma. We evaluated the roles of BRCA associated protein-1 (BAP1) and cyclin-dependent kinase inhibitor 2A (CDKN2A) in colon cancer and mesothelioma to support the hypothesis that BAP-1 and CDKN2A are tumour suppressor genes involved in disease progression, recurrence, or death in both digestive cancers and mesothelioma. Potentially, these markers may be used as predictors of worse prognosis, but we also stress the importance of clinical surveillance of exposed patients because asbestos could induce cancer in any organ.

In plain English

This was a case report of four patients recorded by the mesothelioma register of Apulia, southern Italy. Each had a long history of asbestos exposure and developed both colorectal cancer and mesothelioma. Three patients were exposed only at work (merchant marine deck officer, dressmaker, carpenter). The fourth, a welder, was also exposed through living near an asbestos factory. The article did not report which fiber types these patients were exposed to. Two patients had mesothelioma at the same time as the bowel cancer, and two developed it four years later. Two mesotheliomas were in the pleura and two in the peritoneum. A stain found no asbestos fibres in the bowel tumours, but an asbestos body was seen in abdominal (ascitic) fluid from one patient. Two patients showed loss of BAP1 protein in both their tumours. All eight tumours had CDKN2A gene deletions: mostly heterozygous in bowel tumours and mostly homozygous in mesotheliomas. The authors speculated on a possible common asbestos-linked pathway and called for further molecular study. They noted the small, retrospective series and limited gene testing.

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: Case report (case series of four patients), retrospective, with tissue staining and molecular analysis (BAP1 immunohistochemistry and CDKN2A FISH)
• Who was studied: Four asbestos-exposed patients with colorectal cancer and mesothelioma, from the Apulia regional mesothelioma register (Bari, Italy). Three were men aged 70, 71 and 89, and one was a woman aged 58. Patients 1 and 4 had synchronous mesothelioma (found at the same time). Patients 2 and 3 developed metachronous mesothelioma four years later. Mesotheliomas were pleural in patients 1 and 2 and peritoneal in patients 3 and 4. The bowel cancers were in the colon (patient 1) or rectum (patients 2 to 4).
• Exposure: Asbestos exposure was taken from register questionnaires. The fiber types these patients were exposed to were not reported. Patient 1: occupational, merchant marine deck officer, 1958 to 1989. Patient 2: occupational, dressmaker, 1971 to 1975 and 1980 to 1990. Patient 3: occupational, carpenter, 1960 to 1980. Patient 4: occupational, welder, 1957 to 1975, plus environmental exposure as a resident near an asbestos factory, 1971 to 2018.
• Main results:
  • The Perls' Prussian Blue stain found no asbestos fibres in any of the four colorectal adenocarcinoma samples. An asbestos body was identified in the ascitic fluid cellblock of patient 1.
  • Two patients (patients 1 and 4 in Table 2) showed absence of BAP1 expression in both their intestinal tumour and their mesothelioma.
  • All eight tumours had CDKN2A deletions above the cut-off.
  • In the four intestinal tumours, the median share of cells with heterozygous deletion was 63%, versus 29% with homozygous deletion.
  • In the four mesotheliomas, the pattern was reversed: the median share of cells was 16% for heterozygous deletion and 72.5% for homozygous deletion.
  • Biomarker testing of the colorectal cancers (including mismatch repair protein expression and RAS mutations) found no mutations.
• The authors' conclusion: The authors concluded that asbestos exposure deserves continued attention because asbestos can reach any organ. They said further molecular analysis of tumours in asbestos-exposed patients is warranted to evaluate causality. They also speculated on a possible common asbestos-linked pathway of carcinogenesis.
• Limitations the authors state:
  • Retrospective design and a limited number of cases.
  • Molecular testing was limited to specific targets; other genes, such as NF2, could be involved.
  • The search for asbestos fibres in intestinal cancer samples should be done with electron microscopy coupled with microanalysis.
  • A possible germline BAP1 mutation could not be evaluated because patients did not consent to genetic analyses.
  • Survival could not be compared because of the small number of cases.

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelioma, Colorectal Cancer, Carcinogenesis, Asbestos Exposure, BAP1, CDKN2A, Disease Progression, Prognosis.

Related studies

• Occupational exposures and colorectal cancers: a quantitative overview of epidemiological evidence — E. Oddone, C. Modonesi, et al. (2014)
• Antioxidants in the chemoprevention of colorectal cancer and colorectal adenomas in the general population: a systematic review and meta-analysis — D. Papaioannou, K.L. Cooper, et al. (2011)
• Occupational asbestos exposure and risk of esophageal, gastric and colorectal cancer in the prospective Netherlands Cohort Study — N.S. Offermans, R. Vermeulen, et al. (2014)
• Workplace exposure to diesel and gasoline engine exhausts and the risk of colorectal cancer in Canadian men — L. Kachuri, P.J. Villeneuve, et al. (2016)
• Evidence for excess colorectal cancer incidence among asbestos-exposed men in the Beta-Carotene and Retinol Efficacy Trial — O.A. Aliyu, M.R. Cullen, et al. (2005)
• Clear cell colorectal carcinoma: Time to clarify diagnosis — A. Remo, F. Grillo, et al. (2017)

Browse more research in International Journal of Molecular Sciences, or return to medical research.