Transferrin Receptor Expression in a Nested Case-Control Prostate Cancer Cohort
V Macias, BM Henry, GA Hartung, JR Shah, T Nazir, AK Balla. University of Illinois at Chicago, Chicago, IL
Background: Transferrin receptor (TfR, CD71), a type II transmembrane homodimer glycoprotein (180kDa), regulates the cellular uptake of iron through binding and internalizing iron loaded transferrin. Its expression is related to iron requirements associated with cell proliferation. Overexpression has been demonstrated in cancer cells, including prostate carcinoma (PCa) and is thought to be of prognostic value in breast and colon cancer. We previously reported lower concentrations of iron (Fe) in prostatectomy cases with subsequent biochemical PSA recurrence. The present study evaluates the prognostic significance of TfR expression in PCa cells. In addition, we tested the hypothesis of an association of high TfR expression with low tissue iron.
Design: PCa tumor samples from 40 cases with PSA recurrence matched 1:1 (for year of surgery, race, age, Gleason score and pTNM stage) with samples from 40 cases without recurrence were obtained from an Outcome TMA-based data set from the Cooperative Prostate Cancer Tissue Resource. TMA with 0.6mm cores quadruplicates were immunostained using a mouse monoclonal anti-human transferrin antibody (1:100 dilution; Zymed Laboratories). TfR expression in tumor cells was scored using automated computer-based image analysis software (Aperio Technologies). Case-control results were compared using the Wilcoxon signed pair-matched test for differences in TfR intensity. Statistical correlation between TfR expression and tissue Fe levels was calculated by the Spearman's correlation coefficient rank test.
Results: Data generated by digital scoring was available in 29 complete pairs (n=58). The Wilcoxon signed rank test showed a statistically significant difference of TfR expression between the recurrence and non recurrence, with a higher intensity levels of TfR in the first group (p=0.04). The correlation between TfR expression and Fe concentrations was not statistically significant (rs = - 0.16, p= 0.20, n = 69).
Conclusions: Our results shows that Transferrin Receptor may be a prognostic marker of PCa with biochemical recurrence even after cases are paired by stage, Gleason score, race and age. As a validation set to confirm its value as a prognostic marker, we are now conducting evaluation of additional 320 cases of known outcome.
Category: Genitourinary (including renal tumors)
Wednesday, March 24, 2010 9:30 AM
Poster Session V # 95, Wednesday Morning