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. This study aims to determine the frequency of expression of ER, Rb1 and P16 by Immuno-histochemistry (IHC) in tissue sections prepared from formalin fixed, paraffin embedded tissue blocks of ovarian epithelial tumors.

Epithelial tumor_1

  • A negative correlation between Rb1 and P16 expression in our cohort has been identified which was similar to other studies.
  • The coordinate pattern of negative stain for the three markers Rb1, P16 and ER was seen in 32 % of mucinous carcinomas in contrast to 4, 10, and 10 % of HGSC, LGSC, and ECs, respectively.
  • Rb1+ and ER+ were co-expressed in 19 and 50 % of HGSC and LGSC, respectively and were statistically significant.
  • Higher intensity of ER was observed in LGSC and low in HGSC with statistically significant difference.
  • These patients (Rb1+, ER+) could be a target for CDK4/6 inhibition plus letrozole, with or without antiestrogen therapy.
  • An inverse correlation existed between the Rb1 and P16 expression based on tumor grade with high expression of the Rb1 in low grade tumors in contrast to high expression of P16 in high grade lesions.

Epithelial tumor_2

This information can provide a rational basis for clinical trials that aim to target these proteins.

Citation
Ferguson DC, Long DJ, Smith MC, Craig-Owens LD, Means J, Fadare O, Desouki MM. 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(1):34.

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