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Aquaporin-1 Protein Expression of the Primary Tumor May Predict Cerebral Progression of Cutaneous Melanoma

  • Original Article
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Pathology & Oncology Research

Abstract

Brain metastasis is a frequent complication of the progression of malignant melanoma. In a previous study aquaporin 1 (AQP1) protein expression was found to be associated with increased mortality and decreased progression free survival in cutaneous melanoma. To explore further the potential of this marker we studied the AQP1 protein expression in 67 metastatic melanoma patients using immunohistochemistry. Primary tumor samples were acquired from patients with brain (BR) (n = 44) and extra-cranial (EC) (n = 23) metastases, while brain metastatic samples were collected during neurosurgical resection (n = 5). Patients with brain metastases had shorter overall survival (p = 0.02) and significantly higher AQP1 expression in the primary tumors (median H-score = 250 vs. 140, p = 0.044) as compared to patients of the EC metastasis group. AQP1 expression was found to be significantly lower in the brain metastases compared to the corresponding primary tumors (median H-score = 35 vs. 300 p = 0.01). However, in brain metastases AQP1 expression was heterogenous, AQP1 protein was more abundant in the melanoma cells far away from the capillaries as compared to tumor cells adjacent to vessels indicating a hypoxia-driven expression of AQP1. We suggest that AQP1 expression could well be a prognostic marker of brain metastatic potential of human cutaneous melanoma.

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Fig. 1: Survival analysis of metastatic melanoma patients using Kaplan-Meier statistics.
Fig. 2: AQP1 Protein expression in malignant melanoma.
Fig. 3: Quantitative measurement of AQP1 expression in primary melanomas.
Fig. 4: Comparison of AQP1 expression in primary and corresponding brain metastatic tumors. (n = 5)

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Acknowledgements

We also thank Violetta Piurkó for her valuable contribution in immunohistochemistry. We are grateful for all the patients, their families and the clinicians who participated in this study, and consented to provide tissue for research.

Funding

Support was provided by Hungarian Scientific Research Fund Research Grant K-112371, the NAP_B13-2014- and 2017-1.2.1.NKP-0002 programs.

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Authors and Affiliations

  1. 2nd Department of Pathology, Semmelweis University, Üllői Str 93, Budapest, H-1091, Hungary

    E. Imrédi, I. Kenessey & József Tímár

  2. National Institute of Oncology, Budapest, Hungary

    E. Imrédi, G. Liszkay, V. Plotár & M. Gödény

  3. Department of Dermatology, Venerology and Dermato-Oncology, Budapest, Hungary

    B. Tóth

  4. National Institute of Clinical Neuroscience, Budapest, Hungary

    I. Fedorcsák

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  1. E. Imrédi
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  2. G. Liszkay
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  5. M. Gödény
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Correspondence to József Tímár.

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Ethical Statement

This manuscript has not been published previously. This study is not part of another larger clinical study. We state that no data have been fabricated or manipulated. We also state that the Result section contains our own data. All authors expressed their consent to publish this manuscript in the final form. Authors whose names appear on the submission have contributed sufficiently to this work and therefore share collective responsibility and accountability for the demonstrated results.

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Imrédi, E., Liszkay, G., Kenessey, I. et al. Aquaporin-1 Protein Expression of the Primary Tumor May Predict Cerebral Progression of Cutaneous Melanoma. Pathol. Oncol. Res. 26, 405–410 (2020). https://doi.org/10.1007/s12253-018-0513-6

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  • DOI: https://doi.org/10.1007/s12253-018-0513-6

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