Osteopontin is linked to p65 and MMP-9 expression in pulmonary adenocarcinoma but not in malignant pleural mesothelioma

Our plain-English summary of Osteopontin is linked to p65 and MMP-9 expression in pulmonary adenocarcinoma but not in malignant pleural mesothelioma, by A.B. Frey, A. Wali, H. Pass, et al (Histopathology, 2007).

The study

• Authors: A.B. Frey, A. Wali, H. Pass, F. Lonardo
• Journal: Histopathology
• Published: 2007;50(6):720-6
• Cited by: 19 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Aims: Osteopontin (OPN) is a matricellular protein involved in tissue remodelling, cell-mediated immunity and malignant transformation. High OPN serum levels predict poor prognosis in non-small cell carcinoma and set patients with malignant pleural mesothelioma (MM) apart from disease-free asbestos-exposed individuals. Yet neither the spectrum of tissue expression nor the signalling pathways of OPN in MM and pulmonary adenocarcinoma have been characterized, although in vitro evidence links OPN to the epidermal growth factor receptor (EGFR) pathway. The aim of this study was to address these deficiencies.

Methods And Results: OPN expression was investigated immunohistochemically in 104 adenocarcinomas and 38 MM and correlated with histological features, including tumour type, grade and proliferation and with expression of activated intermediary EGFR signalling pathway molecules p65, p-AKT, p-ERK, p-STAT-3, and of metalloproteinase (MMP)-1, MMP-2 and MMP-9. In MM, OPN expression was widespread (36/38) and independent of the molecular parameters studied. In adenocarcinoma, high OPN expression was correlated with expression of p65, p-ERK and MMP-9.

Conclusions: Frequent OPN expression is typical of, but not specific for MM, whereas it appears to select adenocarcinoma cases with p65 and MMP-9 expression, suggesting a link with EGFR signalling pathways.

In plain English

This laboratory study from a Detroit pathology department examined the protein osteopontin in surgically removed tumour tissue. Samples from 104 lung adenocarcinomas and 38 malignant pleural mesotheliomas were stained to measure osteopontin and compare it with tumour grade, a marker of tumour-cell proliferation, and several signalling and tissue-remodelling proteins. The study did not measure asbestos exposure. Osteopontin was found in 36 of 38 mesotheliomas (95%) and in 76 of the 98 adenocarcinomas that could be scored (78%). In mesothelioma, no correlation was detected with tumour type or the other proteins; the authors said osteopontin's high frequency and levels probably prevented detecting such associations. In adenocarcinoma, high osteopontin was more common in low-grade tumours (66% versus 33% of high-grade tumours) and went together with high levels of p65, p-ERK and MMP-9. The authors concluded that tissue osteopontin is common in mesothelioma but not specific to it, and does not appear to help pathologists tell mesothelioma apart from other tumours. They noted that staining cannot show how the proteins work and that small samples might miss variation within tumours.

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 (immunohistochemistry) study of tissue arrays made from resected tumours
• Who was studied: Tumour samples from 104 lung adenocarcinomas and 38 malignant pleural mesotheliomas (20 epithelioid, 16 biphasic, 2 sarcomatoid) from the files of the authors' department (Detroit, MI); dates of the cases are not given
• Exposure: No asbestos or other exposure was studied; the study measured tissue levels of osteopontin and of p65, p-AKT, p-ERK, p-STAT-3, MMP-1, MMP-2, MMP-9, and Ki67 (a stain assumed to reflect tumour-cell proliferation)
• Main results:
  • Osteopontin was present in 76 of 98 scorable adenocarcinomas (78%) and 36 of 38 mesotheliomas (95%)
  • High osteopontin levels (score 5 to 9) were seen in 23 of 38 mesotheliomas; adenocarcinomas were split 39 low versus 37 high
  • In adenocarcinoma, 66% of low-grade versus 33% of high-grade tumours had a high osteopontin score (P less than or equal to 0.01)
  • In adenocarcinoma (Table 2), high osteopontin was found in 8 (73%) of high-p65 cases versus 31 (37%) of low-p65 cases; in 12 (86%) of high-p-ERK versus 37 (43%) of low-p-ERK cases; and in 28 (72%) of high-MMP-9 versus 11 (20%) of low-MMP-9 cases (table P values: less than or equal to 0.05 for p65, less than or equal to 0.01 for p-ERK and MMP-9)
  • In adenocarcinoma, the average proliferative rate did not differ significantly between low (34%) and high (27%) osteopontin cases, and no correlation was found between osteopontin and p-STAT-3 or p-AKT
  • In mesothelioma, no correlation was detected between osteopontin and tumour type or any of the molecules studied; the authors said the high frequency and high levels of osteopontin probably prevented detection of statistically significant associations
  • In mesothelioma, high MMP-2 was found in 28 of 31 cases and high MMP-9 in 24 of 30 cases
• The authors' conclusion: The authors concluded that high tissue osteopontin is frequent in both mesothelioma and adenocarcinoma, so it is not a specific marker of mesothelioma and does not appear to help in diagnosing it, and that in lung adenocarcinoma osteopontin is linked to the EGFR pathway, particularly p65 and MMP-9
• Limitations the authors state:
  • Immunohistochemistry cannot show how the proteins function; the hypothesis needs biochemical confirmation
  • The small tissue-array samples might miss variation within tumours
  • The high frequency and levels of osteopontin in mesothelioma probably prevented detection of statistically significant associations
  • Missing links in the signalling pathway might reflect low sensitivity of the antibodies used
  • The number of cases that could be studied varied by marker because of uneven tissue cores

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: Osteopontin, Adenocarcinoma, Pleural Mesothelioma, Malignant Transformation, Prognosis, Carcinoma, EGFR.

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• Osteopontin modulates inflammation, mucin production, and gene expression signatures after inhalation of asbestos in a murine model of fibrosis — T. Sabo-Attwood, M.E. Ramos-Nino, et al. (2011)
• Prognostic role of osteopontin expression in malignant pleural mesothelioma — S. Cappia, L. Righi, et al. (2008)
• Osteopontin mRNA expression by rat mesothelial cells exposed to multi-walled carbon nanotubes as a potential biomarker of chronic neoplastic transformation in vitro — S. Sridharan, A. Taylor-Just, et al. (2021)

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