Neurotensin expression and outcome of malignant pleural mesothelioma

Our plain-English summary of Neurotensin expression and outcome of malignant pleural mesothelioma, by M. Alifano, M. Loi, S. Camilleri-Broet, et al (Biochimie, 2010).

The study

• Authors: M. Alifano, M. Loi, S. Camilleri-Broet, S. Dupouy, J.F. Régnard, P. Forgez
• Journal: Biochimie
• Published: 2010;92(2):164-70
• Cited by: 15 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant pleural mesothelioma is a frequently fatal disease and the impact of available treatments is globally poor. Identification of new prognostic factors would help in the understanding of disease progression and, possibly, patient management. Here, we evaluate the prognostic impact of the neurotensin (NTS) and its cognate receptor (NTSR1) known for mediating cellular proliferation, survival, invasiveness, and mobility. We studied a series of 52 consecutive patients with epithelioid malignant mesothelioma undergoing management with curative intent, by immunohistochemistry for the expression of NTS and NTSR1. Specimens were scored as 0, 1, or 2 for less than 10%, between 10 and 50%, or more than 50% of NTS positive staining in tumor cells, respectively. Immunohistochemistry revealed that NTS and NTSR1 expression was found in 71.1% and 90.4% of malignant mesotheliomas, respectively. Using univariate analysis, expression of NTS was significantly (p = 0.015) related with a poor prognosis, with median survivals of 11.0 months, 18.4 months, and 29.8 months in patients showing expression scored as 2, 1, and 0, respectively. Multivariate analysis showed that expression of NTS (p = 0.007) and non-surgical therapy (p = 0.004) were independent predictors of poor prognosis. In order to evaluate the role of NTS/NTSR1 complex in mesothelioma progression, in vitro cell invasion assays and wound healing were performed on the mesothelioma cell line, MSTO-211H, and showed that inhibition of the NTS system resulted in a significant reduction of both migration and collagen invasion of mesothelioma cells. The expression of NTS is identified as a prognostic marker in patients with malignant pleural mesothelioma (Patent EP 08305971.7).

2009 Elsevier Masson SAS. All rights reserved.

In plain English

This study examined whether neurotensin (NTS), a signalling molecule, and its receptor (NTSR1) in tumor tissue were linked to survival in malignant pleural mesothelioma. The authors retrospectively reviewed 52 consecutive patients with epithelioid mesothelioma treated with curative intent at Hôtel-Dieu Hospital, Paris, between 2002 and 2006. Of these patients, 65% had work exposure to asbestos. NTS was found in 37 of 52 tumors (71.1%) and NTSR1 in 47 of 52 (90.4%). NTSR1 expression, as measured by tissue staining, was not associated with survival in these patients. Tumors were scored 0, 1 or 2 by the share of tumor cells staining for NTS (under 10%, 10 to 50%, over 50%). Median survival was 29.8, 18.4 and 11 months for scores 0, 1 and 2. In multivariate analysis, NTS expression and the absence of extrapleural pneumonectomy were independent predictors of poor 5-year survival. In univariate analysis, survival did not differ by asbestos exposure. In laboratory tests on a mesothelioma cell line, blocking the NTS system did not change cell growth but reduced invasion and migration. The authors concluded that the NTS/NTSR1 complex is a potential marker of negative prognosis and a putative mediator of disease progression.

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 review of hospital patients, with tumor immunohistochemistry and survival analysis, plus laboratory (in vitro) experiments on a mesothelioma cell line
• Who was studied: 52 consecutive patients (34 men, 18 women) with epithelioid malignant pleural mesothelioma treated at Hôtel-Dieu Hospital, Paris, 2002 to 2006. The comparison group was 26 patients with recurrent idiopathic spontaneous pneumothorax. Laboratory work used the MSTO-211H mesothelioma cell line.
• Exposure: The study examined a tumor marker (neurotensin and its receptor), not asbestos exposure. Work exposure to asbestos was recorded in 65% of patients. Fiber types and doses were not reported.
• Main results:
  • Among the 52 mesothelioma patients, NTS expression was found in 37 (71.1%): 20 tumors scored 1 and 17 scored 2.
  • Among the 52 mesothelioma patients, NTSR1 expression was found in 47 (90.4%).
  • In pleura from the 26 pneumothorax patients, NTS was seen in 8 (31%) and NTSR1 in 20 (77%).
  • In the mesothelioma patients, NTSR1 expression as assessed by immunohistochemistry was not associated with survival. The authors' wording was 'no impact on survival'.
  • In the mesothelioma patients, median survival was 29.8, 18.4 and 11 months for NTS scores 0, 1 and 2. The article reports this difference as statistically significant (p = 0.015).
  • Five-year survival was 33.3% in patients with no NTS expression.
  • Five-year survival was 0% in patients whose NTS staining was scored 2.
  • In univariate analysis of the mesothelioma patients, survival did not differ by sex, age or asbestos exposure.
  • Patients treated by extrapleural pneumonectomy showed a trend toward better prognosis that did not reach statistical significance in univariate analysis (p = 0.075). Their 5-year survival was 42.3%, compared with 11.0% for patients not receiving this surgery.
  • In multivariate analysis, NTS expression and the absence of extrapleural pneumonectomy were independent predictors of poor 5-year survival.
  • In the MSTO-211H cell line, the NTSR1 blocker SR48692 had no effect on cell growth.
  • In the MSTO-211H cell line, 4% of cells treated with SR48692 and 5% of cells treated with NTS-blocking antibody invaded collagen. In the control groups, 13% of untreated cells and 11% of DMSO-treated cells did so.
  • In the wound healing test on MSTO-211H cells, the remaining gap was 48% of the original with SR48692 treatment. With the control treatments it was 27% (untreated) and 30% (DMSO).
• The authors' conclusion: The authors concluded that the NTS/NTSR1 complex is not only a potential marker of negative prognosis but also a putative mediator of disease progression in mesothelioma.
• Limitations the authors state:
  • Tumor stage (TNM) was not included in the multivariate analysis because too few patients fell into each category.
  • Post-operative treatment and follow-up did not follow a uniform protocol.

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, Disease Progression, Epithelioid, Malignant Mesothelioma, Immunohistochemistry, Prognosis, Median Survival, Multivariate Analysis.

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