PreImplantation Factor immunohistochemical expression correlates with prostate cancer aggressiveness

Maria Rosaria Raspollini, Ilaria Montagnani, Paolo Cirri, Gianna Baroni, Alessia Cimadamore, Marina Scarpelli, Liang Cheng, Antonio Lopez-Beltran, Rodolfo Montironi, Eytan R. Barnea

Research output: Contribution to journalArticle


Background: The PreImplantation Factor (PIF)—a peptide secreted by viable embryos—exerts autotrophic protective effects, promotes endometrial receptivity and controls trophoblast invasion. Synthetic PIF (sPIF) has both immune-protective and regenerative properties, and reduces oxidative stress and protein misfolding. PIF is detected by immunohistochemistry (IHC) in hyperplastic endometriotic lesions and advanced uterine cancer. sPIF reduces graft-versus-host disease while maintaining a graft-versus-leukemia effect. Methods: PIF detection in prostate cancer was assessed in 50 human prostate samples following radical prostatectomy using tumor-microarray-based IHC correlating PIF immune staining with Gleason score (GS) and cancer aggressiveness. Results: PIF was detected in moderate-to-high risk prostate cancer (GS 4+3 and beyond, prognostic groups 3 to 5). In prostate cancer (GS (WHO Grade Group (GG)5), PIF was detected in 50% of cases; in prostate cancer (GS 4+4 GG4), PIF was observed in 62.5% of cases; in prostate cancer (GS 4+3 GG3), PIF immunostaining was observed in 57.1% of cases. In prostate cancer, (GS 3+4 GG2) and (GS 3+3 GG1) cases where PIF staining was negative to weak, membranous staining was observed in 20% of cases (staining pattern considered negative). High-grade prostate intraepithelial neoplasia PIF positive stain in 28.57% of cases (6 of 21) was observed. In contrast, PIF was not detected in normal prostate glands. Importantly, sPIF added to the PC3 cell line alone or combined with prostate cancer fibroblast feeder-cells did not affect proliferation. Only when peripheral blood mononuclear cells were added to the culture, a minor increase in cell proliferation was noted, reflecting local proliferation control. Conclusions: Collectively, PIF assessment could be a valuable, simple-to-use immunohistochemical biomarker to evaluate aggressiveness/prognosis in specimens from prostate cancer patients.

Original languageEnglish (US)
Pages (from-to)82-90
Number of pages9
JournalInternational Journal of Biological Markers
Issue number2
StatePublished - 2020


  • cancer aggressiveness
  • Gleason score
  • immunohistochemistry
  • preimplantation factor (PIF)
  • Prostate cancer

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Oncology
  • Clinical Biochemistry
  • Cancer Research

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  • Cite this

    Raspollini, M. R., Montagnani, I., Cirri, P., Baroni, G., Cimadamore, A., Scarpelli, M., Cheng, L., Lopez-Beltran, A., Montironi, R., & Barnea, E. R. (2020). PreImplantation Factor immunohistochemical expression correlates with prostate cancer aggressiveness. International Journal of Biological Markers, 35(2), 82-90.