title: Comparative analysis of Rb1, P16 and ER as diagnostic, prognostic and potential targets for therapeutic agents in ovarian epithelial tumors: an immunohistochemical study of 130 ovarian carcinomas.
abstract: BACKGROUND
  Deregulation of CDK4/6, cyclin D/P16 and retinoblastoma (Rb) are known aberrations in certain malignancies. There has been a recent interest in exploring the combination of letrozole and CDK4/6 inhibitors in recurrent ER+ ovarian cancers.
  
  
  METHODS
  This study aimed to determine the frequency of expression of Rb1, P16 and ER in ovarian epithelial tumors by immunohistochemistry.
  
  
  RESULTS
  Co-expression of all 3 markers studied was seen in 10% of high grade serous carcinoma (HGSC) and low grade serous carcinoma (LGSC). Coordinate expression of Rb1+ and ER+ in HGSC and LGSC was seen in 67% of grade 1/2 vs. 44 % of grade three tumors (p < 0.05). The reverse was true with positive P16 staining in 73% of grade three vs. 32% of grade 1/2 tumors (p < 0.001).
  
  
  CONCLUSIONS
  Coordinate pattern of Rb1+ and ER+ in HGSC and LGSC is 19 and 50%, respectively. Rb1 and P16 show inverse expression pattern according to tumor grade with more frequent Rb1 in low grade vs. more frequent P16 in grade 3 tumors. These data provide a rational basis for clinical trials that aim to target these proteins.
authors.affiliation: Department of Pathology Microbiology and Immunology, Vanderbilt University School of Medicine, 1161 21st Avenue South, MCN, C-2310A, Nashville, TN, 37232-2561, USA. donna.c.ferguson@vanderbilt.edu.
authors.forename: Donna Catherine
authors.initials: DC
authors.lastname: Ferguson
authors.affiliation: Department of Pathology Microbiology and Immunology, Vanderbilt University School of Medicine, 1161 21st Avenue South, MCN, C-2310A, Nashville, TN, 37232-2561, USA. daniel.long@Vanderbilt.edu.
authors.forename: Daniel Jerad
authors.initials: DJ
authors.lastname: Long
authors.affiliation: Department of Pathology Microbiology and Immunology, Vanderbilt University School of Medicine, 1161 21st Avenue South, MCN, C-2310A, Nashville, TN, 37232-2561, USA. megan.c.smith@Vanderbilt.edu.
authors.forename: Megan Christine
authors.initials: MC
authors.lastname: Smith
authors.affiliation: Department of Pathology Microbiology and Immunology, Vanderbilt University School of Medicine, 1161 21st Avenue South, MCN, C-2310A, Nashville, TN, 37232-2561, USA. laura.d.craig-owens@vanderbilt.edu.
authors.forename: Laura Deeanne
authors.initials: LD
authors.lastname: Craig-Owens
authors.affiliation: Department of Tennessee Oncology, Sarah Cannon Research Institute, Franklin, TN, USA. jmeanspowell@tnonc.com.
authors.forename: Julie
authors.initials: J
authors.lastname: Means
authors.affiliation: Department of Pathology, University of California San Diego, San Diego, CA, USA. ofadare@mail.ucsd.edu.
authors.forename: Oluwole
authors.initials: O
authors.lastname: Fadare
authors.affiliation: Department of Pathology Microbiology and Immunology, Vanderbilt University School of Medicine, 1161 21st Avenue South, MCN, C-2310A, Nashville, TN, 37232-2561, USA. mokhtar.desouki@vanderbilt.edu.
authors.forename: Mohamed Mokhtar
authors.initials: MM
authors.lastname: Desouki
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D000077216:Carcinoma, Ovarian Epithelial; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis* / Q000235:genetics; D047628:Estrogen Receptor alpha / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D016160:Retinoblastoma Protein / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D016160:Retinoblastoma Protein