Expression of Progesterone Receptor A as an Independent Negative Prognosticator for Cervical Cancer

Int J Mol Sci. 2023 Feb 1;24(3):2815. doi: 10.3390/ijms24032815.

Abstract

The role of progesterone receptor A (PRA) for the survival outcome of cervical cancer patients is ambiguous. In mouse models, it has been shown that PRA plays a rather protective role in cancer development. The aim of this study was to assess its expression by immunohistochemistry in 250 cervical cancer tissue samples and to correlate the results with clinicopathological parameters including patient survival. PRA expression was positively correlated with the International Federation of Gynecology and Obstetrics (FIGO) classification scores. PRA was significantly overexpressed in adenocarcinomas compared to squamous epithelial carcinoma subtypes. Correlation analyses revealed a trend association with the HPV virus protein E6, a negative correlation with p16 and a positive correlation with EP3. PRA expression was also associated with the expression of RIP140, a transcriptional coregulator that we previously identified as a negative prognostic factor for survival in cervical cancer patients. Univariate survival analyses revealed PRA as a negative prognosticator for survival in patients with cervical adenocarcinoma. Multivariate analyses showed that simultaneous expression of RIP140 and PRA was associated with the worst survival, whereas with negative RIP140, PRA expression alone was associated with the best survival. We can therefore assume that the effect of nuclear PRA on overall survival is dependent upon nuclear RIP140 expression.

Keywords: FIGO; HPV E6; RIP140; cervical cancer; negative prognosticator; p16; progesterone receptor A.

MeSH terms

  • Adenocarcinoma* / pathology
  • Animals
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Squamous Cell* / pathology
  • Female
  • Humans
  • Mice
  • Receptors, Progesterone / genetics
  • Uterine Cervical Neoplasms* / pathology

Substances

  • progesterone receptor A
  • Receptors, Progesterone
  • Biomarkers, Tumor

Grants and funding

This research was funded by the Medical Faculty of the University Augsburg, Doctoral Funding Program for Fabian Garrido and supported by the “Heuer Stiftung” for Bernd P. Kost.