Usefulness of Aquaporin 1 as a Prognostic Marker in a Prospective Cohort of Malignant Mesotheliomas

Our plain-English summary of Usefulness of Aquaporin 1 as a Prognostic Marker in a Prospective Cohort of Malignant Mesotheliomas, by J. Driml, E. Pulford, D. Moffat, et al (International Journal of Molecular Sciences, 2016).

The study

• Authors: J. Driml, E. Pulford, D. Moffat, C. Karapetis, S. Kao, K. Griggs, D.W. Henderson, S. Klebe
• Journal: International Journal of Molecular Sciences
• Published: 2016;17(7)
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

(1) BACKGROUND: Malignant mesothelioma (MM) is an aggressive tumour of the serosal membranes, associated with exposure to asbestos. Survival is generally poor, but prognostication for individual patients is difficult. We recently described Aquaporin 1 (AQP1) as independent prognostic factor in two separate retrospective cohorts of MM patients. Here we assess the usefulness of AQP1 prospectively, and determine the inter-observer agreement in assessing AQP1 scores; (2) METHODS: A total of 104 consecutive cases of MM were included. Sufficient tissue for immunohistochemistry was available for 100 cases, and these cases were labelled for AQP1. Labelling was assessed by two pathologists. Complete clinical information and follow up was available for 91 cases; (3) RESULTS: Labelling of ≥50% of tumour cells for AQP indicated improved prognosis in a univariate model (median survival 13 versus 8 months, p = 0.008), but the significance was decreased in a multivariate analysis. Scoring for AQP1 was robust, with an inter-observer kappa value of 0.722, indicating substantial agreement between observers; (4) CONCLUSION: AQP1 is a useful prognostic marker that can be easily incorporated in existing diagnostic immunohistochemical panels and which can be reliably interpreted by different pathologists.

In plain English

This prospective study at Flinders Medical Centre in South Australia included 104 consecutive patients diagnosed with or reviewed for malignant mesothelioma between 2010 and 2013. Tumour tissue from 100 cases was stained for Aquaporin 1 (AQP1), a water-channel protein. Two pathologists scored labelling against a cutoff of 50% of tumour cells. Survival information covered 91 patients, mostly men (71) and mostly with pleural mesothelioma (85). In a single-factor (univariate) analysis, AQP1 status was linked to survival (p = 0.008). After adjusting for age, sex and tumour subtype, the link was not statistically significant (p = 0.233). Median survivals were 13 months (95% CI 7.9 to 18) and 8 months (95% CI 4 to 12). The abstract, figure and conclusion give the longer survival to patients with 50% or more labelling, but one results paragraph reverses this. High labelling was far more common in epithelioid than in sarcomatoid or biphasic tumours. The sarcomatoid subtype stayed linked to poorer survival after adjustment (p = 0.014). The pathologists agreed substantially (kappa 0.772 in the text, 0.722 in the abstract). Asbestos exposure was not reported. The authors concluded that AQP1 is a useful, reliably scored prognostic marker.

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: Prospective cohort study of consecutive mesothelioma cases, with tissue staining (immunohistochemistry) and survival analysis (Kaplan-Meier and Cox regression); published as a short 'Communication'
• Who was studied: 104 consecutive patients with malignant mesothelioma diagnosed or reviewed at Flinders Medical Centre, South Australia, from 2010 to 2013. 100 had enough tissue for AQP1 staining, and 91 had complete clinical follow-up. Of those 91 patients, the median age was 71 years (range 40 to 91); 71 were male and 20 female; 85 had pleural and 6 peritoneal mesothelioma; 66 tumours were epithelioid, 11 biphasic and 14 sarcomatoid.
• Exposure: The study did not measure or report asbestos exposure. The factor studied was the percentage of tumour cells showing membrane labelling for Aquaporin 1 (AQP1), divided at 50%. The survival groups are less than 50% versus 50% or more. The scoring section instead describes the split as 50% or less versus more than 50%.
• Main results:
  • Among the 91 patients with follow-up, AQP1 status was significantly associated with survival in univariate Cox regression (p = 0.008), but not in the multivariate model (p = 0.233). In the table, the hazard ratio for patients with fewer than 50% labelled cells was 1.830 in univariate analysis and 1.367 in multivariate analysis, compared with patients above 50%.
  • Median survival was 13 months (95% CI 7.9 to 18) in one AQP1 group and 8 months (95% CI 4 to 12) in the other. The abstract, the Figure 1 legend, the hazard ratios and the conclusion give 13 months to patients with 50% or more labelling (n = 44). The results paragraph instead gives 13 months to the group below 50% (n = 47).
  • Across the 100 stained cases, the authors reported that 70% of epithelioid mesotheliomas had AQP1 scores of 50% or more, compared with 7% of sarcomatoid and 8% of biphasic tumours. The table counts are 50 of 72 epithelioid, 1 of 14 sarcomatoid and 2 of 14 biphasic cases.
  • Median survival was 13.5 months for epithelioid, 4.6 months for biphasic (4.5 in Table 5) and 2 months for sarcomatoid mesothelioma. Sarcomatoid subtype remained significant in the multivariate model (p = 0.014). Age at or above the median of 71 years was associated with poorer survival in univariate (p = 0.014) and multivariate (p = 0.007) analysis.
  • The kappa statistic for agreement between the two pathologists scoring AQP1 was 0.772 in the body of the article (0.722 in the abstract), described as substantial agreement.
  • The six peritoneal mesotheliomas, all epithelioid, did not show significantly different survival from the pleural cases. Median survival was 9 months for both; mean survival was 13.6 months for pleural and 20.7 months for peritoneal cases.
  • Sex was not associated with survival in this cohort. Treatment (surgery, chemotherapy, radiotherapy) was also not significantly associated with overall survival.
• The authors' conclusion: The authors concluded that AQP1 is a useful prognostic marker in mesothelioma that can be scored reliably, with substantial agreement between observers. They reported significantly better survival for patients with 50% or more AQP1 expression in univariate analysis. In multivariate analysis, they stated, AQP1 expression could not be separated from the sarcomatoid subtype.
• Limitations the authors state:
  • Only six peritoneal mesotheliomas were included, so the comparison of AQP1 scores between pleural and peritoneal cases rests on very few cases.
  • Most of the cohort received conservative treatment, which the authors suggest may explain why treatment was not linked to survival.
  • The authors suggest that the lack of a sex difference in survival may reflect gender bias, that is, the different frequency of mesothelioma in men and women.
  • Only one representative slide was scored per case, and most cases were diagnostic biopsies with only one tissue block available.

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: Mesothelioma, Immunohistochemistry, Prognosis, Median Overall Survival, Multivariate Analysis.

Related studies

• Aquaporin 1 is an independent prognostic factor in pleural malignant mesothelioma — S.C. Kao, N. Armstrong, et al. (2012)
• Immunohistochemical Expression of Aquaporin-1 in Fluoro-Edenite-Induced Malignant Mesothelioma: A Preliminary Report — G. Angelico, R. Caltabiano, et al. (2018)
• 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)
• Aquaporins 1, 3 and 5 in Different Tumors, their Expression, Prognosis Value and Role as New Therapeutic Targets — M.S. Moosavi, Y. Elham (2020)
• 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)
• Gene expression profile of aquaporin 1 and associated interactors in malignant pleural mesothelioma — R. Jagirdar, E.I. Solenov, et al. (2013)

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