title: Expression of Hypoxia-Inducible Factor 1α in Invasive Breast Cancer with Metastasis to Lymph Nodes: Correlation with Steroid Receptors, HER2 and EPO-R.
abstract: BACKGROUND
  Expression of hypoxia-inducible factor 1α (HIF-1α) reflects the degree of cell hypoxia and its increased expression was found in most neoplasms, their metastasis as well as in some precancerous lesions.
  
  
  OBJECTIVE
  The study aimed to investigate the expression HIF-1α in invasive breast cancer with metastasis to lymph nodes in correlation with steroid receptors (ER-estrogen receptor, PR-progesterone receptor), HER2 (human epidermal growth factor receptor 2) and EPO-R (erythropoietin receptor).
  
  
  METHODS
  A total of 58 cases of invasive breast cancer with metastasis to lymph nodes were assessed for expression of HIF-1α, EPO-R, ER, PR and HER2.
  
  
  RESULTS
  In our study, among all invasive breast cancers, 36.2% exhibited HIF-1α expression in the nuclei of neoplastic cells. We also assessed the correlation between histological type of cancer and basic immunohistochemical profile that included HIF-1α expression and statistical significance was noted only in the case of PR-/ER-/HER2-/ /HIF-1α-/ and PR+/ER+/HER2-/HIF-1α-/ (p = 0.028 and p = 0.008, respectively). However, only in the case of the PR+/ER+/HER2-/HIF-1α+/ immunohistochemical profile and histological grading did we note a statistical significance (p = 0.006). Expression of HIF-1α was most often noted in cancers exhibiting expression of HER2 protein (57.14%). Our study also assessed the relationship between the expression of HIF-1α in invasive breast cancers and the expression of EPO-R and areas of necrosis, demonstrating a statistically significant dependence (p = 0.003).
  
  
  CONCLUSIONS
  Expression of HIF-1α was more often noted in invasive HER2+ cancers characterized by high degree of aggressiveness and poorer prognosis, which might suggest that presence of HIF-1α protein expression in HER2+ cancers could be an additional prognostic factor, the frequent occurrence of the phenotype of HIF-1α and EPO-R in cancers invasive HER2 +, in the absence of ER and PR, may suggest that HIF-1α and EPO-R may be an indicator of the aggressiveness of invasive breast cancers, indicating the need for a specific forms of treatment in this group of patients.
authors.affiliation: Department of Human Biophysics and Physiology, Medical University of Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Badowska-Kozakiewicz
authors.affiliation: Department of Human Biophysics and Physiology, Medical University of Warsaw, Poland.
authors.forename: Maria
authors.initials: M
authors.lastname: Sobol
authors.affiliation: Department of Pathomorphology, Military Institute of Health Services, Warszawa, Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Patera
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis / Q000096:biosynthesis*; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000096:biosynthesis*; D017467:Receptors, Erythropoietin / Q000032:analysis / Q000096:biosynthesis; D011960:Receptors, Estrogen / Q000032:analysis / Q000096:biosynthesis; D011980:Receptors, Progesterone / Q000032:analysis / Q000096:biosynthesis
chemical_list: D014408:Biomarkers, Tumor; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D018719:Erb-b2 Receptor Tyrosine Kinases; D017467:Receptors, Erythropoietin; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C497442:HIF1A protein, human; C508053:ERBB2 protein, human
keywords: EPO-R; HER2; HIF-1α; breast cancer; steroid receptors