Prognostic role of osteopontin expression in malignant pleural mesothelioma

Our plain-English summary of Prognostic role of osteopontin expression in malignant pleural mesothelioma, by S. Cappia, L. Righi, D. Mirabelli, et al (American Journal of Clinical Pathology, 2008).

The study

• Authors: S. Cappia, L. Righi, D. Mirabelli, P. Ceppi, E. Bacillo, F. Ardissone, L. Molinaro, G.V. Scagliotti, M. Papotti
• Journal: American Journal of Clinical Pathology
• Published: 2008;130(1):58-64
• Cited by: 36 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant pleural mesothelioma (MPM) represents highly aggressive neoplasms with a mean survival of approximately 10 months. Osteopontin, a glycoprotein involved in cell-matrix interactions correlated with invasion and metastatic spread in several tumors, has recently been proposed as a serum marker of MPM in asbestos-exposed subjects. The aim of this study was to define the prognostic role of osteopontin in MPM. For the study, 32 long-term survivors (>24 months) and a random sample of 69 short-term survivors (<or=24 months) were matched according to the main clinicopathologic features. Immunohistochemical osteopontin expression in tissue specimens was quantified through the HScore (histologic scoring) method and correlated with clinicopathologic parameters and survival. Osteopontin expression was significantly lower in long-term compared with short-term survivors (P< .0001), and overall survival analysis showed that low osteopontin expression was associated with longer survival; multivariate analysis confirmed the value of osteopontin expression as an independent prognostic factor (P< .0001).

In plain English

This study from St Luigi Hospital in Turin, Italy, examined whether the amount of a protein called osteopontin in tumor tissue was linked to survival in malignant pleural mesothelioma. From 394 cases diagnosed between 1989 and 2003, the authors studied 32 patients who lived more than 24 months and 69 randomly selected patients who lived 24 months or less. The two groups were matched on sex, age, asbestos exposure, disease stage and tumor type. Biopsy tissue was stained and scored from 0 to 300. Scores were lower in long-term survivors (median 50) than in short-term survivors (median 180), and the difference was statistically significant. In an analysis that accounted for other factors, patients scoring 145 or higher had a hazard ratio of 3.47 (interval printed as 1.97 to 6.14) compared with lower scorers. Osteopontin was the only factor that stayed significant in that analysis. Osteopontin levels showed no significant correlation with asbestos exposure. Normal pleural lining cells did not stain, but reactive non-cancerous lining cells stained weakly. The authors concluded that osteopontin expression may be a predictive marker of survival at diagnosis. Serum samples were not available.

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 study comparing all eligible long-term survivors with a matched random sample of short-term survivors, using immunohistochemical staining of archived tumor tissue, plus a separate consecutive series and non-cancer control samples
• Who was studied: Patients with malignant pleural mesothelioma diagnosed at the University of Turin Division of Pathology, St Luigi Hospital, Turin, Italy, 1989 to 2003 (394 cases). 70 long-term survivors were identified and 32 were retained. 69 short-term survivors were randomly selected and matched (at least 2 per long-term case). A further 81 consecutive cases (January 2005 to June 2007) and 8 non-malignant pleural control samples were also studied.
• Exposure: The main variable studied was osteopontin expression in tumor tissue, scored by the HScore method (0 to 300). Asbestos exposure (presence, level, type and duration) was used to match the groups. Fiber types were not reported. 21 of 32 long-term survivors had an asbestos exposure history. Among the 51 of 69 short-term survivors with exposure information, all but 1 were exposed.
• Main results:
  • Osteopontin HScore ranged from 5 to 250 (median 50) in the long-term survivor group and from 30 to 297 (median 180) in the short-term survivor group (P < .0001, Mann-Whitney U).
  • In the pooled long- and short-term groups (101 patients), osteopontin HScore of 145 or higher versus below 145 had a hazard ratio of 3.67 (range printed as 2.28-5.89) in univariate analysis. In multivariate analysis it had a hazard ratio of 3.47 (1.97-6.14), P < .00001. Median survival in the table was 27.8 for the 50 low-score patients and 12.1 for the 51 high-score patients.
  • Osteopontin was the only factor that remained significant in multivariate analysis.
  • In univariate analysis, performance status was also a significant prognostic factor (P = .02), but it did not remain significant in multivariate analysis.
  • In the long- and short-term groups, osteopontin expression had no significant correlation with sex, age, asbestos exposure, thoracoscopic stage or histologic type. It was significantly correlated with weight loss (P = .04), performance status (P = .006) and time from symptoms to diagnosis (P = .004).
  • HScore values in the pooled long- and short-term groups (median 145) did not differ significantly from those in the 81 consecutive cases (median 132; P = .3817).
  • Normal mesothelial cells from patients with pneumothorax showed no osteopontin staining. Reactive mesothelial cells in non-malignant chronic pleuritis showed weak staining.
• The authors' conclusion: The authors concluded that increased osteopontin expression levels may be a predictive marker of survival at the time of mesothelioma diagnosis. They proposed that osteopontin expression be considered as a stratification factor in future treatment trials.
• Limitations the authors state:
  • Serum samples were not available, so circulating (blood) osteopontin could not be measured. Only tissue from paraffin blocks was studied.
  • The 24-month cutoff separating long- and short-term survival was set arbitrarily.
  • Osteopontin was also detected in reactive or hyperplastic mesothelial lesions. The authors said this limits its proposed diagnostic role, at least in tissue.

Topics

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

Medical terms in this study, explained in our Lexicon: Osteopontin, Pleural Mesothelioma, Neoplasm, Glycoprotein, Overall Survival, Multivariate Analysis.

Related studies

• 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)
• Osteopontin is linked to p65 and MMP-9 expression in pulmonary adenocarcinoma but not in malignant pleural mesothelioma — A.B. Frey, A. Wali, et al. (2007)
• 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)
• Osteopontin, GLUT1 and Ki-67 expression in malignant peritoneal mesothelioma: prognostic implications — Y. Liu, G. Zheng, et al. (2021)
• Utility of osteopontin and serum mesothelin in malignant pleural mesothelioma diagnosis and prognosis assessment — B.D. Grigoriu, A. Scherpereel, et al. (2007)
• Mesothelin and osteopontin as circulating markers of diffuse malignant peritoneal mesothelioma: A preliminary study — F. Bruno, D. Baratti, et al. (2018)

Browse more research in American Journal of Clinical Pathology, or return to medical research.