Selective downregulation of STAT1 expression in the neoplastic cells of human breast tumors. (A) Representative image of STAT1 staining on normal breast tissues of healthy individuals (n = 5) shows STAT1 expression in luminal epithelial cells and stromal cells and occasionally in myoepithelial cells. Original magnification, 100×. Scale bar = 200 μm. Inset, 400×. (B) Representative image of a breast tumor case with high levels of STAT1 expression in both the epithelial and stromal compartments. Original magnification, 200×. Scale bar = 100 μm. Inset, 400×. (C-F) Representative images of paired adjacent normal breast tissues (left) with breast tumors (right; n = 11). Morphologically normal breast tissues from patients with breast cancer display a STAT1 expression pattern that is similar to that in normal breasts from healthy individuals (C, E). Panel (C) is the paired normal tissue of the tumor in panel (D) (case 87), whereas panel (E) is the paired normal tissue of the tumor in panel (F) (case 58). The epithelial tumor cells of the representative estrogen receptor-alpha-positive (ERα+) (D) and ERα- (F) breast cancers were devoid of STAT1 expression, whereas STAT1 level remained high in the tumor stroma. Original magnification, 200×. Scale bars = 100 μm. (G) Intensity scores of the neoplastic and stromal cells of all cases (n = 161) are plotted. Reduced STAT1 staining intensity was preferentially associated with ERα+ human breast cancers relative to ERα- breast cancers in both the neoplastic and stromal compartments (P = 0.001, unpaired t test). Stromal cells had an overall higher STAT1 expression level than the neoplastic cells of the same tumors (P < 0.0001, Wilcoxon signed rank test). (H) Breast tumors exhibited significant reduction in STAT1 score in comparison with matched normal breast tissues (n = 11) (P = 0.003, Wilcoxon signed rank test). STAT1 score is the sum of the score representing the percentages of STAT1+ cells (percentage score) and that representing the STAT1 staining intensity (intensity score).