Figure 9. BRCA1-mutated breast cancer samples (from 9 out of 10 patients examined) also show a loss of Cav-1 and high MCT4 expression in cancer-associated fibroblasts, with elevated mitochondrial mass in the epithelial cancer cell compartment. Human breast cancer samples from BRCA1-mutated patients were immunostained with anti-Cav-1, MCT4 or TOMM20 antibodies. Note that stromal cells display the loss of Cav-1 expression, with high MCT4 expression. Cav-1 expression in endothelial cells serves as an internal positive control (arrows), as it is not normally downregulated. Conversely, epithelial cancer cells show very high TOMM20 expression relative to adjacent stromal tissue. TOMM20 is a well-established marker of mitochondrial mass. These observations are indicative of the onset of oxidative stress, autophagy and glycolysis in the tumor microenvironment, with enhanced mitochondrial biogenesis in BRCA1-mutated breast cancer cells. Consistent with the idea that the tumor stroma is glycolytic, the cancer-associated fibroblasts are MCT4(+) and TOMM20(-). Conversely, the BRCA1-mutated epithelial cancer cells are MCT4(-) and TOMM20(+), reflective of oxidative mitochondrial metabolism. Finally, loss of stromal Cav-1 staining is an established marker of autophagy in the tumor microenvironment. Original magnification, 40x.