IFI16 Protein: A Potential Molecular Marker in Prostate Cancer: From Molecular Lab to the Pathology Lab
JP Reynolds, HX Bui, H Al-Ghawi, GA Hill, R Panchananthan, D Choubey. VAMC & U of Cincinnati, Cincinnati, OH
Background: Protein markers which predict progression of prostate cancer (PC) to a higher grade/stage such as overexpression of TMPRSS2 may help manage PC effectively. Interferon inducible IFI16 is a human member of the p200-protein family. Because increased expression of IFI16 protein in normal prostate epithelial cells (PrEC) inhibits cell proliferation, we investigated whether expression of IFI16 protein in the prostate could serve as a marker for low and high grade/stage PC.
Design: Expression of IFI16 protein was compared in total cell lysates from cultured normal (PrEC), a benign prostate hyperplasia cell line (BPH-1) and derivatives from the BPH1 cell line that have acquired the ability to form tumors in nude mice (aggressive lines) and PC cell lines (RWPE-1, DU-145, PC-3 and LNCaP). Human prostate tissue array slides (Imgenex) containing 98 prostate samples and 30 of our archival cases (total 45 BPH, 29 Gleason Score(GS)>6, 26 GS7, 24 GS<8, and 4 metastatic PC to bone marrow and lymph nodes) were stained with H&E and IHC for IFI16 (goat polyclonal sc-6050 Santa Cruz Biotech) and p63 (Ventana pre-dilute). All prostatic tissue arrays and our own cases were reviewed independently by two pathologists to agree on GS and rate IHC intensity and percentage of glands staining for IFI16 on a scale of 0(no stain) to 2(highest). Expression of p63 was used as a control in cell cultures and tissue IHC.
Results: Expression of IFI16 protein is detectable in normal PrECs and in a BPH cell line; however, IFI16 is reduced or lost in more aggressive BPH1 and most human PC cell lines tested. As a control p63 was lost in all PC cells and tissue.
Tissue expressed IFI16 in BPH and low grade PC; most high grade PC and metastasis lost staining (p=0.0003).
IHC for IFI16 #of cases (% of cases)
Conclusions: Loss of IFI16, a marker of cellular senescence, in human prostate tissue is associated with a higher grade/stage PC, including metastases to other organs. IFI16 may be implicated in the actual progression from a low to high grade/stage PC. Further studies are warranted.
Category: Genitourinary (including renal tumors)
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 133, Monday Morning