Aquaporin 1 is an independent prognostic factor in pleural malignant mesothelioma

Our plain-English summary of Aquaporin 1 is an independent prognostic factor in pleural malignant mesothelioma, by S.C. Kao, N. Armstrong, B. Condon, et al (Cancer, 2012).

The study

• Authors: S.C. Kao, N. Armstrong, B. Condon, K. Griggs, B. McCaughan, S. Maltby, A. Wilson, D.W. Henderson, S. Klebe
• Journal: Cancer
• Published: 2012;118(11):2952-61
• Cited by: 41 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Malignant mesothelioma (MM) is an aggressive cancer of serosal membranes, mostly pleura. It is related to asbestos exposure and its incidence in most industrialized countries is projected to remain stable or to increase until 2020. Prognosis remains poor. Clinical prognostic scoring systems lack precision. No prognostic tissue markers are available. Aquaporin 1 (AQP1) is a cell membrane channel involved in water transport, cell motility, and proliferation. A blocker and an agonist are available.

Methods: Two independent cohorts of MM were studied. Cohort 1 consisted of 80 consecutive patients who underwent radical surgery (extrapleural pneumonectomy [EPP]). Cohort 2 included 56 conservatively managed patients from another institution. Clinical information was obtained from files. Diagnoses were histologically verified. Immunohistochemical labeling for AQP1 was performed on tumor tissue and the percentage of positive cells was scored.

Results: We demonstrated expression of AQP1 in normal and neoplastic mesothelium at the apical aspect of the cell, in keeping with a role in water transport. For both cohorts, expression of AQP1 by ≥50% of tumor cells was associated with significantly enhanced survival (9.4 months vs 30.4 months in EPP patients and 5 months vs 15 months in conservatively treated patients). This was independent of established prognostic factors, including histologic subtype, pathologic stage, sex, and age at time of diagnosis.

Conclusion: Expression of AQP1 correlated significantly with prognosis in MM, irrespective of treatment or established prognostic factors. Immunohistochemical labeling for AQP1 should be included in the routine histopathologic workup. An agonist or blocker may become useful for treatment.

Copyright © 2011 American Cancer Society.

In plain English

This Australian study asked whether tumor levels of the water-channel protein aquaporin 1 (AQP1) were linked to survival in malignant mesothelioma. The authors stained tumors from two groups: 80 patients who had radical surgery (extrapleural pneumonectomy) in Sydney, and 56 patients managed without major surgery at Flinders Medical Centre. The article did not report individual patients' asbestos exposure histories. Patients with AQP1 in 50% or more of tumor cells lived longer. Median survival was 30.4 months (95% CI 21.4-39.4) versus 9.4 months (3.3-15.4) in the surgical group, and 15 months (4.3-25.7) versus 5 months (2.2-7.8) in the non-surgical group. After adjustment, AQP1 below 50%, compared with 50% or more, remained significant in both groups, with hazard ratios for death of 2.14 (95% CI 1.15-3.96) and 2.66 (1.16-6.11). Histologic subtype did not remain significant. Adding AQP1 to age, sex and subtype gave what the authors called a moderate gain in predictive accuracy. A trend toward larger pleural effusions with more AQP1 was not statistically significant. The authors concluded AQP1 assessment should be routine and named the small sample (136 patients) as a limitation.

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: Study of tumor tissue from two independent patient cohorts (a testing cohort and a validation cohort), with immunohistochemical labeling for AQP1 and survival analysis (Kaplan-Meier and Cox models)
• Who was studied: 136 patients with malignant mesothelioma in Australia. Testing cohort: 80 consecutive patients who had extrapleural pneumonectomy at Royal Prince Alfred and Strathfield Private Hospitals, Sydney, 1994 to November 2009. Validation cohort: 56 conservatively managed patients diagnosed at Flinders Medical Centre, 1998 to July 2010.
• Exposure: Individual patients' asbestos exposure histories were not reported. The article mentions asbestos only as the general cause of mesothelioma. The factor studied was the percentage of tumor cells labeling for aquaporin 1 (AQP1), compared as under 50% versus 50% or more.
• Main results:
  • Surgical (EPP) cohort: median overall survival was 9.4 months (95% CI 3.3-15.4) for AQP1 scores under 50% and 30.4 months (95% CI 21.4-39.4) for scores of 50% or more
  • Conservatively managed (Flinders) cohort: median overall survival was 5 months (95% CI 2.2-7.8) for AQP1 scores under 50% and 15 months (95% CI 4.3-25.7) for scores of 50% or more
  • Surgical cohort, multivariate analysis: AQP1 score under 50% (versus 50% or more) had a hazard ratio of 2.14 (95% CI 1.15-3.96), P = .02. Sex and calretinin score also remained significant, and histologic subtype and pathologic stage did not.
  • Conservatively managed cohort, multivariate analysis: AQP1 score under 50% (versus 50% or more) had a hazard ratio of 2.66 (95% CI 1.16-6.11), P = .02, and was the only significant variable
  • In the conservatively managed cohort, mean AQP1 score differed significantly by subtype: 61.8% for epithelial, 12.9% for biphasic and 10.8% for sarcomatoid tumors. In the surgical cohort there was no significant difference by subtype.
  • Among 46 conservatively managed patients with effusion data, there was a trend to larger pleural effusions with higher AQP1 expression, but it was not statistically significant
  • Adding AQP1 to age, sex and histologic subtype increased explained variation in survival from 5.8% to 13.4% (surgical cohort) and from 13.3% to 18.0% (conservatively managed cohort). The authors described the gain in predictive accuracy as only moderate.
  • In normal mesothelium, AQP1 was located at the apical (surface) side of the cells, confirmed by immuno-electron microscopy. In tumor cells this apical pattern was not always kept.
• The authors' conclusion: The authors concluded that AQP1 labeling in 50% or more of tumor cells was an independent predictor of longer survival in both cohorts, regardless of treatment. In their opinion, AQP1 assessment should be part of routine histologic work-up for malignant mesothelioma.
• Limitations the authors state:
  • The relatively small number of patients (136), which the authors nonetheless considered reasonable for an uncommon tumor
  • The effusion-size analysis may have lacked statistical significance because the number of cases was too small

Topics

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

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Pleura, Asbestos Exposure, Prognosis, Extrapleural Pneumonectomy (EPP), Mesothelium, Histological Subtype.

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• Challenges and controversies in the diagnosis of malignant mesothelioma: Part 2. Malignant mesothelioma subtypes, pleural synovial sarcoma, molecular and prognostic aspects of mesothelioma, BAP1, aquaporin-1 and microRNA — D.W. Henderson, G. Reid, et al. (2013)
• Blockade of aquaporin 1 inhibits proliferation, motility, and metastatic potential of mesothelioma in vitro but not in an in vivo model — S. Klebe, K. Griggs, et al. (2015)
• Immunohistochemical Expression of Aquaporin-1 in Fluoro-Edenite-Induced Malignant Mesothelioma: A Preliminary Report — G. Angelico, R. Caltabiano, et al. (2018)
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• Aquaporins 1, 3 and 5 in Different Tumors, their Expression, Prognosis Value and Role as New Therapeutic Targets — M.S. Moosavi, Y. Elham (2020)

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