Pleural mesotheliomas have an integrin profile distinct from visceral carcinomas

Our plain-English summary of Pleural mesotheliomas have an integrin profile distinct from visceral carcinomas, by G.K. Koukoulis, J. Shen, R. Monson, et al (Human Pathology, 1997).

The study

• Authors: G.K. Koukoulis, J. Shen, R. Monson, W.H. Warren, I. Virtanen, V.E. Gould
• Journal: Human Pathology
• Published: 1997;28(1):84-90
• Cited by: 19 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Cryosections of epithelial, sarcomatoid, and biphasic malignant mesotheliomas (EMM, n = 11; SMM, n = 5; BMM, n = 6) of the pleura were immunostained with monoclonal antibodies to integrin subunits alpha 1-6 and v, and beta 1-4. Localization patterns were compared with those known to occur in pulmonary and other adenocarcinomas (PADC, ADC). EMM and the epithelial component of BMM (ecBMM) expressed alpha 1,3,5,6, and v and beta 1 and 4. SMM and the sarcomatoid elements of BMM (scBMM) reacted variably for alpha 1,3,5,6 and v, and beta1. Reactions for alpha3, found in all tumors, were strongest in EMM, ecBMM, and PADC. Our findings indicate that EMM and ecBMM parallel PADC and most ADC in their expression of alpha6 beta4, underscoring that this laminin integrin receptor is intimately associated with these neoplastic epithelial phenotypes. Also, our observations on alpha3 beta1 suggest that this cell-cell adhesion-mediating integrin is related to the epithelial phenotype. Notably, all malignant mesotheliomas (MM), including those with distinct glandular structures, expressed the alpha5 beta1 fibronectin receptor, thus paralleling most sarcomas and differing from PADC and most other ADC. We conclude that irrespective of architectural and cytologic variants, transformed mesothelial cells possess an integrin repertory that differs significantly from that of most ADC, including those of the lung. These findings set mesothelium apart from epithelia and may prove helpful as adjunct tools for the differential diagnosis between EMM and AD.

In plain English

This laboratory study stained tumor tissue from 22 pleural malignant mesotheliomas removed at surgery in Chicago (11 epithelial, 5 sarcomatoid, 6 biphasic) for integrins, which are proteins on the cell surface that bind cells to surrounding tissue. The authors compared the results with previously published findings for adenocarcinomas of the lung and other organs. The article did not discuss asbestos. In epithelial tumors and the epithelial parts of biphasic tumors, the alpha5 integrin subunit stained moderately to strongly in all cases, and alpha6 and beta4 were also present. In sarcomatoid tumors, alpha5 stained moderately to strongly in four of five cases. Beta4 was not detected in sarcomatoid tumors or in the sarcomatoid parts of biphasic tumors. The authors concluded that mesothelioma cells have an integrin profile distinct from most adenocarcinomas, including those of the lung, because of the consistent presence of the alpha5 beta1 fibronectin receptor. They suggested this may help pathologists tell epithelial mesothelioma apart from adenocarcinoma. They noted that two proteins appearing in the same place does not prove that they interact.

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: Laboratory pathology study (immunohistochemistry on surgically removed tumor tissue), compared with previously published data on carcinomas
• Who was studied: 22 pleural malignant mesotheliomas (11 epithelial, 5 sarcomatoid, 6 biphasic). Tissue was obtained immediately after surgical removal at Rush-Presbyterian-St Luke's Medical Center, Chicago. Study dates were not given.
• Exposure: No asbestos or other exposure was studied or reported. The study examined staining for integrin subunits alpha 1 to 6, alpha v and beta 1 to 4 in tumor tissue.
• Main results:
  • Epithelial mesotheliomas (including the epithelial component of biphasic tumors): moderate to strong alpha5 staining in all cases
  • Epithelial mesotheliomas: consistently intense alpha6 staining, and moderately strong but uneven beta4 staining, both at the cell-matrix interface
  • Epithelial mesotheliomas: minimal and focal alpha2 staining in 2 of 11 cases (weak alpha1 staining was also reported in 2 of 11)
  • Sarcomatoid mesotheliomas: moderate to strong alpha5 staining in four of five cases. The one tumor without alpha5 expressed only alpha v beta1.
  • Sarcomatoid mesotheliomas: moderate alpha6 staining in three of five tumors
  • Sarcomatoid mesotheliomas: generally strong and uniform beta1 staining in all cases
  • No beta4 staining in pure sarcomatoid tumors or in the sarcomatoid component of biphasic tumors. Beta4 was present around glands in biphasic tumors.
• The authors' conclusion: The authors concluded that, given the consistent presence of the alpha5 beta1 fibronectin receptor, the integrin profile of pleural mesotheliomas is distinct from that of virtually all carcinomas that pose diagnostic problems. They concluded that these findings may help as additional tools for distinguishing epithelial mesothelioma from adenocarcinoma.
• Limitations the authors state:
  • Finding alpha5 beta1 and EDA-cellular fibronectin in the same location does not prove that the two interact. The authors stated that clarifying this would require additional studies, including in vitro analysis.

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, Carcinoma, Sarcomatoid, Biphasic Mesothelioma, Malignant Mesothelioma, Pleura, Monoclonal, Adenocarcinoma.

Related studies

• Immunolocalization of integrins in the normal lung and in pulmonary carcinomas — G.K. Koukoulis, W.H. Warren, et al. (1997)
• Vitronectin enhances internalization of crocidolite asbestos by rabbit pleural mesothelial cells via the integrin alpha v beta 5 — A.M. Boylan, D.A. Sanan, et al. (1995)
• Role of alphavbeta5 integrin receptor in endocytosis of crocidolite and its effect on intracellular glutathione levels in human lung epithelial (A549) cells — P. Pande, T.A. Mosleh, et al. (2006)
• Distinct DNA methylation profiles in malignant mesothelioma, lung adenocarcinoma, and non-tumor lung — J.A. Tsou, L.Y. Shen, et al. (2005)
• Carbon Nanotube and Asbestos Exposures Induce Overlapping but Distinct Profiles of Lung Pathology in Non-Swiss Albino CF-1 Mice — E.A. Frank, V.S. Carreira, et al. (2016)
• Distinct keratin patterns demonstrated by immunoperoxidase staining of adenocarcinomas, carcinoids, and mesotheliomas using polyclonal and monoclonal anti-keratin antibodies — H.J. Kahn, P.S. Thorner, et al. (1986)

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