title: Expression of regulatory proteins and proliferative activity in relation to phenotypic characteristics of upper urothelial carcinoma.
abstract: OBJECTIVE
  Deregulation of the normal cell cycle is common in upper urothelial carcinoma (UUC). The aim of this study was to investigate the expression of regulatory proteins of the cell cycle (p53, p16, cyclin D1, HER-2) and proliferative Ki-67 activity in UUC, and to determine their interaction and influence on the phenotypic characteristics of UUC.
  
  
  METHODS
  In 44 patients with UUC, histopathological and immunohistochemical analyses (p53, p16, cyclin D1, HER-2, and Ki-67) of tumors were done.
  
  
  RESULTS
  Overexpression/altered expression of p53, p16, cyclin D1 or HER-2 was detected in 20%, 57%, 64%, and 57% of tumors, respectively. Eleven (25%) UUC had a high proliferative Ki-67 index. Forty patients (91%) had at least one marker altered, while four (9%) tumors had a wild-type status. Analysis of relationship between expressions of molecular markers showed that only high expression of p53 was significantly associated with altered p16 activity (p < 0.05). High Ki-67 index was associated with the high stage (p < 0.005), solid growth (p < 0.01), high grade (p < 0.05), and multifocality p < 0.05) of UUC, while high expression of p53 was associated with the solid growth (p < 0.05). In regression models that included all molecular markers and phenotypic characteristics, only Ki-67 correlated with the growth (p < 0.0001), stage (p < 0.01), grade (p < 0.05) and multifocality (p < 0.05) of UCC; (Ki-67 and HER-2 expression correlated with the lymphovascular invasion (p < 0.05).
  
  
  CONCLUSIONS
  This investigation showed that only negative regulatory proteins of the cell cycle, p53 and p16, were significantly associated in UUC, while proliferative marker Ki-67 was in relation to the key phenotypic characteristics of UUC in the best way.
authors: University of Pristina-Kosovska Mitrovica, School of Medicine, Pristina, Serbia.
authors: Zana
authors: Z
authors: Dolićanin
authors: Ljubinka Janković
authors: LJ
authors: Velicković
authors: Biljana
authors: B
authors: Djordjević
authors: Milan
authors: M
authors: Visnjić
authors: Ivana
authors: I
authors: Pesić
authors: Ana
authors: A
authors: Ristić
authors: Vesna
authors: V
authors: Marjanović
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002295:Carcinoma, Transitional Cell / Q000378:metabolism / Q000473:pathology*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D007680:Kidney Neoplasms / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D010641:Phenotype; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014516:Ureteral Neoplasms / Q000378:metabolism / Q000473:pathology*; D055815:Young Adult
chemical_list: D018797:Cell Cycle Proteins; D019938:Cyclin D1; D019941:Cyclin-Dependent Kinase Inhibitor p16; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53; C000614131:CDKN2A protein, human; C508053:ERBB2 protein, human