title: Mitochondrial UCP4 and bcl-2 expression in imprints of breast carcinomas: relationship with DNA ploidy and classical prognostic factors.
abstract: 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.
authors.affiliation: 1st Pathology Department and Cytology Unit, National & Kapodistrian University of Athens, Medical School, 75 Mikras Asias, 11527 Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Gonidi
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: Athanassiadou
authors.forename: Efstratios
authors.initials: E
authors.lastname: Patsouris
authors.forename: Angelos
authors.initials: A
authors.lastname: Tsipis
authors.forename: Stavros
authors.initials: S
authors.lastname: Dimopoulos
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Kyriakidou
authors.forename: George
authors.initials: G
authors.lastname: Chelidonis
authors.forename: Pauline
authors.initials: P
authors.lastname: Athanassiadou
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry* / Q000235:genetics / Q000556:secondary / Q000601:surgery; D018275:Carcinoma, Lobular / Q000737:chemistry* / Q000235:genetics / Q000556:secondary / Q000601:surgery; D002454:Cell Differentiation; D016009:Chi-Square Distribution; D005260:Female; D006115:Greece; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D016015:Logistic Models; D008207:Lymphatic Metastasis; D026901:Membrane Transport Proteins / Q000032:analysis*; D008875:Middle Aged; D000071245:Mitochondrial Uncoupling Proteins; D009367:Neoplasm Staging; D011003:Ploidies; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D018570:Risk Assessment; D012307:Risk Factors; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D026901:Membrane Transport Proteins; D000071245:Mitochondrial Uncoupling Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53; C117577:SLC25A27 protein, human; C495901:TP53 protein, human; C508053:ERBB2 protein, human