The relationship between the tumor cell expression of hypoxic markers and survival in patients with ER-positive invasive ductal breast cancer

Shamis, S. A.K., Quinn, J. , Mallon, E. E.A., Edwards, J. and McMillan, D. C. (2022) The relationship between the tumor cell expression of hypoxic markers and survival in patients with ER-positive invasive ductal breast cancer. Journal of Histochemistry and Cytochemistry, 70(7), pp. 479-494. (doi: 10.1369/00221554221110280) (PMID:35792080)

Abstract

The prognostic significance of hypoxia markers, hypoxia-inducible factor-1α (HIF-1α), hypoxia-inducible factor-2α (HIF-2α), and carbonic anhydrase IX (CAIX), was investigated in estrogen receptor (ER)-positive breast cancer patients. Immunohistochemistry determined the expression of makers in two independent ductal ER-positive cohorts (Training set, n=373 and Validation set, n=285) and was related to clinicopathological parameters and disease-free survival (DFS). In the training cohort, nuclear HIF-1α (1) was independently associated with poorer DFS in luminal A tumors [hazard ratio (HR) = 0.53 95% confidence interval (CI): 0.30–0.94, p=0.030]. In the validation cohort, both HIF-1α (1) and CAIX were independently associated with decreased DFS in the entire cohort (HR = 1.85 95% CI: 1.10–3.11, p=0.019; HR = 1.74 95% CI: 1.08–2.82, p=0.023), in luminal A disease (HR = 1.98 95% CI: 1.02–3.83, p=0.042), and in luminal B disease (HR = 2.75 95% CI: 1.66–4.55, p<0.001), respectively. Taken together, elevated cytoplasmic HIF-1α (1) expression was an independent prognostic factor in luminal A disease, whereas CAIX was an independent prognostic factor in luminal B disease. Further work in large tissue cohorts is required.

• Item Type: Articles
• Additional Information: This research was funded by Libyan government and Libyan Cultural Affairs Bureau, grant number AA274-518-54090.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Quinn, Dr Jean and McMillan, Professor Donald and Mallon, Dr Elizabeth and Edwards, Professor Joanne and Shamis, Suad Ahmad Khalifa
• Authors: Shamis, S. A.K., Quinn, J., Mallon, E. E.A., Edwards, J., and McMillan, D. C.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: Journal of Histochemistry and Cytochemistry
• Publisher: SAGE Publications
• ISSN: 0022-1554
• ISSN (Online): 1551-5044
• Published Online: 06 July 2022
• Copyright Holders: Copyright © 2022 The Authors
• First Published: First published in Journal of Histochemistry and Cytochemistry 70(7): 479-494
• Publisher Policy: Reproduced under a Creative Commons License

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