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

J Ovarian Res. 2015 Jun 5:8:34. doi: 10.1186/s13048-015-0163-1.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / biosynthesis*
  • Biomarkers, Tumor / genetics
  • Carcinoma, Ovarian Epithelial
  • Cyclin-Dependent Kinase Inhibitor p16 / biosynthesis*
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • Estrogen Receptor alpha / biosynthesis*
  • Estrogen Receptor alpha / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Neoplasm Staging
  • Neoplasms, Glandular and Epithelial / genetics*
  • Neoplasms, Glandular and Epithelial / pathology
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology
  • Prognosis
  • Retinoblastoma Protein / biosynthesis*
  • Retinoblastoma Protein / genetics

Substances

  • Biomarkers, Tumor
  • Cyclin-Dependent Kinase Inhibitor p16
  • ESR1 protein, human
  • Estrogen Receptor alpha
  • Retinoblastoma Protein