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

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.

Aquaporin‐1 expression in fluoro‐edenite‐induced mesothelioma effusions: An approach by cell‐block procedure

“…Namely, a statistically significant association of AQP‐1 high expression with increased survival was observed with a median OS of 12 months for patients with ≥50% AQP‐1 expression vs a median OS of only 7 months for patients with less than 50% AQP‐1 expression. The relationship between higher levels of AQP‐1 in MM and a better prognosis confirms the results of previous studies, but appears to be in conflict with data reported in other tumours, including breast cancer, melanoma, urothelial carcinoma and pharyngeal squamous cell carcinoma, in which increased levels of AQP1 are associated with a poorer prognosis . These data and the relatively few studies on MM require further validation.…”

“…Cytological and IHC assessments of MM through specific panels of antibodies are available, but prognostic markers are less numerous and not routinely used in MM effusions. Recent studies have reported a potential prognostic significance of AQP‐1 in surgical MM samples . In the current study, we performed an IHC evaluation of AQP1 expression in a cohort of MM patients, living nearby the area of Biancavilla.…”

“…Many diagnostic biomarkers are used for MM diagnosis, such as calretinin, CK5, podoplanin, mesothelin, osteopontin and others, but prognostic predictors are not routinely applied . Recently, aquaporin 1 (AQP‐1), a water channel protein found in cell membranes which facilitates transcellular water transport, has been hypothesised to be an independent prognostic factor in pleural MM patients . The availability of a prognostic marker for MM is important because, despite a low median survival (6‐12 months), the survival of MM patients ranges between 1.5 and 60 months .…”

Immunohistochemical Expression of Aquaporin-1 in Fluoro-Edenite-Induced Malignant Mesothelioma: A Preliminary Report

“…The most important prognostic parameters for MPM include the histological subtype, sex and age at diagnosis [ 4 ]. Recent studies have highlighted the potential role of aquaporin-1 (AQP1) as an independent prognostic factor for improved survival in MPM patients exposed to asbestos [ 5 , 6 ]. AQP1 is a water channel protein found in cell membranes throughout the body and facilitates transcellular water transport [ 7 , 8 ].…”

The Effect of Aquaporin 1-Inhibition on Vasculogenic Mimicry in Malignant Mesothelioma

“…This is potentially significant in MM, which commonly presents with large pleural effusions, which interfere with breathing and thus contribute to poor quality of life. Retained expression of AQP1 by immunohistochemistry in MM histology specimens has been associated with better overall survival, indicating a potential role in pathogenesis [ 23 , 24 ]. Furthermore, increased AQP1 protein and mRNA expression have been observed in epithelioid MM subtypes, which have a better prognosis when compared to biphasic and sarcomatoid subtypes [ 24 , 25 ].…”