Mitochondrial UCP4 and bcl-2 expression in imprints of breast carcinomas: relationship with DNA ploidy and classical prognostic factors.

Mitochondria are the bioenergetic and metabolic centers of cells and play an important role in the regulation of cell death. The mitochondrial apoptosis pathway is controlled by the bcl-2 protein family. Overexpression of mitochondrial uncoupling protein 4 (UCP4) can promote proliferation and inhibit apoptosis and differentiation. Imprint smears obtained from 124 tumors were studied immunocytochemically, and results were correlated with prognostic markers. There were 112 ductal and 12 lobular carcinomas. The positivity of UCP4 was correlated with lymph node metastases (p=0.005), positive ER and PR expression (p<0.0001 for both), as well as positivity for p53 (p<0.0001) and Ki-67 (p<0.0001). Decreased expression of bcl-2 correlated with increased expression of UCP4 (p=0.001). Regarding DNA ploidy, UCP4 positivity was correlated with aneuploid tumors (p=0.002). Negative expression of bcl-2 was correlated with poorly differentiated carcinomas (p<0.0001), as well as with positive expression of p53 (p<0.0001) and Ki-67 (p<0.0001). Logistic regression revealed that ploidy and p53 expression had an impact on UCP4. These findings encourage future investigations regarding the potential role of UCPs not only into mechanisms underlying breast cancer, but also as a novel candidate to the design and development of more effective therapeutic strategies.