Differential expression of extracellular matrix constituents and cell adhesion molecules between malignant pleural mesothelioma and mesothelial hyperplasia

Our plain-English summary of Differential expression of extracellular matrix constituents and cell adhesion molecules between malignant pleural mesothelioma and mesothelial hyperplasia, by G. Alì, N. Borrelli, G. Riccardo, et al (Journal of Thoracic Oncology, 2013).

The study

• Authors: G. Alì, N. Borrelli, G. Riccardo, A. Proietti, S. Pelliccioni, C. Niccoli, L. Boldrini, M. Lucchi, A. Mussi, G. Fontanini
• Journal: Journal of Thoracic Oncology
• Published: 2013;8(11):1389-95
• Cited by: 25 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Introduction: Malignant pleural mesothelioma (MPM) is a highly aggressive neoplasm associated with asbestos exposure. Currently, the molecular mechanisms that induce MPM development are still unknown. The purpose of this study was to identify new molecular biomarkers for mesothelial carcinogenesis.

Methods: We analyzed a panel of 84 genes involved in extracellular matrix remodeling and cell adhesion by polymerase chain reaction (PCR) array in 15 samples of epithelioid mesothelioma and 10 samples of reactive mesothelial hyperplasia (MH; 3 of 25 samples were inadequate for mRNA analysis). To validate the differentially expressed genes identified by PCR array, we analyzed 27 more samples by immunohistochemistry, in addition to the 25 samples already studied.

Results: Twenty-five genes were differentially expressed in MPM and MH by PCR array. Of these we studied matrix metalloproteinase 7 (MMP7), MMP14, CD44, and integrin, alpha3 expression by immunohistochemistry in 26 epithelioid MPM and 26 MH samples from the entire series of 52 cases. We observed higher MMP14 and integrin, alpha3 expression in MPM samples compared with MH samples (p = 0.000002 and p = 0.000002, respectively). Conversely, CD44 expression was low in most (57.7%) mesothelioma samples but only in 11.5% of the MH samples (p = 0.0013). As regards MMP7, we did not observe differential expression between MH and MPM samples.

Conclusions: We have extensively studied genes involved in cell adhesion and extracellular matrix remodeling in MPM and MH samples, gaining new insight into the pathophysiology of mesothelioma. Moreover, our data suggest that these factors could be potential biomarkers for MPM.

In plain English

This laboratory study from Pisa, Italy, compared surgical tissue from 26 patients with epithelioid malignant pleural mesothelioma and 26 patients with reactive mesothelial hyperplasia, a benign condition. All had surgery between January 2006 and September 2012. The article does not report the patients' asbestos exposure. The authors first measured the activity of 84 genes involved in cell adhesion and in the tissue framework around cells, using a subset of samples (13 mesothelioma and 9 hyperplasia samples were usable). Twenty-five genes differed at least fourfold between the groups, and eight of these differences were statistically significant. The authors then stained all 52 samples for four proteins. MMP14 and ITGA3 were each high in 20 of 26 mesothelioma samples (76.9%) but in only 3 of 26 hyperplasia samples (11.5%). CD44 was lower in mesothelioma (p = 0.0013), although the article's text and its table give different percentages for this. MMP7 did not differ between the groups. The authors concluded that MMP14, ITGA3 and CD44 could be biomarkers of mesothelioma. They called the CD44 finding preliminary and noted that the MMP7 gene result was not confirmed by staining.

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 laboratory study of archived surgical tissue samples, using gene expression testing (PCR array) followed by immunohistochemistry (protein staining)
• Who was studied: 26 patients with epithelioid malignant pleural mesothelioma (21 men, 5 women; age 35 to 83, median 66.5) and 26 patients with reactive mesothelial hyperplasia (22 men, 4 women; age 17 to 87, median 63). All had consecutive surgery at the Unit of Thoracic Surgery, University of Pisa, Italy, January 2006 to September 2012. The gene array subset was 15 mesothelioma and 10 hyperplasia samples, of which 3 were inadequate, leaving 13 mesothelioma and 9 hyperplasia samples.
• Exposure: Not studied. The study compared tissue types (epithelioid mesothelioma versus reactive mesothelial hyperplasia). The article does not report the patients' asbestos exposure, fiber types or jobs.
• Main results:
  • In the gene array subset (13 mesothelioma, 9 hyperplasia samples), 25 of 84 genes showed at least a fourfold expression difference between groups. The text says 12 genes were higher and 13 lower in mesothelioma.
  • Eight genes differed with statistical significance. COL16A1 (40.6851-fold), ITGB4, ITGA3 and MMP14 were higher in mesothelioma. CD44, ITGAM, MMP10 and MMP7 were lower in mesothelioma.
  • In staining of all 52 samples, MMP14 and ITGA3 were each high in 20 of 26 epithelioid mesothelioma samples (76.9%) and in 3 of 26 hyperplasia samples (11.5%). The p value was 0.000002 for each.
  • CD44 staining differed significantly between groups (p = 0.0013) and was lower in mesothelioma. The text says CD44 was low or negative in 57.7% of mesothelioma samples and 11.5% of hyperplasia samples. Table 4 instead shows low CD44 in 20 of 26 mesothelioma samples (76.9%) and 8 of 26 hyperplasia samples (30.8%).
  • MMP7 staining did not differ between groups (p = 0.8864). It was low in 13 of 26 (50.0%) samples in each group.
• The authors' conclusion: The authors concluded that patients with mesothelioma had significantly higher MMP14 and ITGA3 expression and lower CD44 expression than patients with mesothelial hyperplasia, suggesting these factors could be biomarkers of malignant pleural mesothelioma.
• Limitations the authors state:
  • The lower MMP7 gene activity in mesothelioma was not confirmed by staining. The authors said further studies are needed on MMP7.
  • The authors described the CD44 difference found by PCR array as a preliminary observation needing further investigation.

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: Pleural Mesothelioma, Reactive Mesothelial Hyperplasia, Neoplasm, Asbestos Exposure, Biomarker, Carcinogenesis, Epithelioid, Mesothelioma.

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