Fig. 4. HIF1A levels and downstream effectors are increased in brain metastases versus primary breast tumors.
a Representative sections showing Brx-82 brain or breast tumor histology after staining with hematoxylin and eosin; or with anti-HIF1A antibody (brown) and counter-stained with hematoxylin. Scale bars: 70 μm. Images are representative of four tumor samples. b Quantitation of nuclear HIF1A staining in Brx-82 and Brx-142 brain and breast tumors, as determined by automated immunohistochemical staining quantitation (n = 1000). Median normalized staining with interquartile range displayed. P values (Brx-82: 5.21 × 10−206; Brx-142: 1.28 × 10−242) calculated by two-tailed unpaired t-test. c Heat map representing the fold change of Brx-82 brain tumors relative to breast tumors for select HIF1A downstream effectors involved in general hypoxic response, glycolysis, and angiogenesis. d Representative sections of matched patient brain metastasis and primary breast tumor histology after staining with hematoxylin and eosin; or with anti-HIF1A antibody (brown) and counter-stained with hematoxylin. Scale bars: 70 μm. Samples displayed are from Patient 4. Images are representative of one tumor sample. e Quantitation of nuclear HIF1A staining in matched patient brain metastases and primary breast tumors, as determined by automated immunohistochemical staining quantitation (Patient no. 3 breast: n = 262; all other samples: n = 1000). Bars represent median, 25th percentile, and 75th percentile normalized staining. P values (Patient 1: <1 × 10−300; Patient 2: 1.39 × 10−36; Patient 3: 8.49 × 10−87; Patient 4: 2.89 × 10−23; Patient 5: <1 × 10−300; Patient 6: 5.08 × 10−93) calculated by two-tailed unpaired t-test. f Heat map representing the fold change of select HIF1A downstream effectors for general hypoxic response, glycolysis, and angiogenesis in patient brain metastases relative to unmatched primary breast tumors30. ***P < 0.001. Source data are provided as a Source Data file.