title: Analysis of p53, p16(INK4a), pRb and Cyclin D1 expression and human papillomavirus in primary ovarian serous carcinomas.
abstract: OBJECTIVE
  To evaluate the prognostic relevance of key cell cycle regulatory proteins p53, p16(INK4a), pRb and Cyclin D1 expression, the presence of high risk HPVs and their association with clinicopathological parameters and the clinical follow up in ovarian cancer patients.
  
  
  METHODS
  53 cases of primary ovarian serous carcinomas were immunohistochemically examined for the expression of p53, p16(INK4a), pRb and Cyclin D1 proteins. Tumor DNA was extracted from paraffin blocks and subjected to HPV 16 and 18 testing. The association between HPV 16 and 18 E6 oncoprotein and cell cycle proteins expression in ovarian carcinomas also was evaluated by immunohistochemistry.
  
  
  RESULTS
  We demonstrated that a majority of moderately and poorly differentiated ovarian carcinomas are characterized by strong expression of p53 and p16(INK4a) proteins. In contrast, strong staining with cyclin D1 antibody was observed in well differentiated tumors. The correlation between strong p53, pRb, Cyclin D1 and clinical stages of disease was also observed. We show that patients with high positivity for p53, p16(INK4a) and Cyclin D1 had a poor prognosis and reduced overall survival. The presence of HPV 16/18 DNA was detected in 17% of ovarian carcinomas. The tumor tissues that reacted positively to HPV E6 antibody in focal and diffuse manners had also significantly low p53 expression profile.
  
  
  CONCLUSIONS
  These findings suggest that p53, p16(INK4a) and Cyclin D1 expression and HPV infection may represent a promising tool toward the identification of ovarian cancer patients with poorer prognosis and shorter survival who might therefore need a more aggressive therapy and HPV screening.
authors.affiliation: RE Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Kyiv 03022, Ukraine. lenabilyk@gmail.com
authors.forename: O O
authors.initials: OO
authors.lastname: Bilyk
authors.forename: N T
authors.initials: NT
authors.lastname: Pande
authors.forename: L G
authors.initials: LG
authors.lastname: Buchynska
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D052685:Alphapapillomavirus / Q000302:isolation & purification*; D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor / Q000032:analysis; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000032:analysis; D019938:Cyclin D1 / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis* / Q000235:genetics; D004268:DNA-Binding Proteins / Q000032:analysis; D005260:Female; D052162:Human papillomavirus 16 / Q000302:isolation & purification; D052161:Human papillomavirus 18 / Q000302:isolation & purification; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000032:analysis; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D030361:Papillomavirus Infections / Q000150:complications / Q000821:virology; D011379:Prognosis; D012097:Repressor Proteins / Q000032:analysis; D016160:Retinoblastoma Protein / Q000032:analysis* / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000032:analysis* / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004268:DNA-Binding Proteins; C068651:E6 protein, Human papillomavirus type 16; C052603:E6 protein, Human papillomavirus type 18; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1