Open AccessThe Relationship Between the Tumor Cell Expression of Hypoxic Markers and Survival in Patients With ER-positive Invasive Ductal Breast Cancer
Author(s) -
Suad Ahmad Khalifa Shamis,
Jean A. Quinn,
Elizabeth E A Mallon,
Joanne Edwards,
Donald C. McMillan
Publication year - 2022
Publication title -
journal of histochemistry and cytochemistry/the journal of histochemistry and cytochemistry
Language(s) - English
Resource type - Journals
eISSN - 1551-5044
pISSN - 0022-1554
DOI - 10.1369/00221554221110280
Subject(s) - hazard ratio , medicine , cohort , immunohistochemistry , breast cancer , oncology , estrogen receptor , ductal carcinoma , cancer , pathology , hypoxia (environmental) , hif1a , tumor hypoxia , confidence interval , radiation therapy , angiogenesis , chemistry , organic chemistry , oxygen
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.