Tumor infiltrating B-cells are increased in prostate cancer tissue

Jason R. Woo, Michael A. Liss, Michelle T. Muldong, Kerrin Palazzi, Amy Strasner, Massimo Ammirante, Nissi Varki, Ahmed Shabaik, Stephen Howell, Christopher J. Kane, Michael Karin, Christina A.M. Jamieson

Research output: Contribution to journalArticle

64 Scopus citations

Abstract

Background: The presence of increased B-cell tumor infiltrating lymphocytes (TILs) was seen in mouse prostate cancer (PCa) but has not been fully documented in human PCa. We, therefore, investigated the density of infiltrating B cells within human PCa utilizing a quantitative computational method. Methods: Archived radical prostatectomy specimens from 53 patients with known clinical outcome and D'Amico risk category were obtained and immunohistochemically (IHC) stained for the B cell marker, CD20. Slides were reviewed by a genitourinary pathologist who manually delineated the tumoral regions of PCa. Slides were digitally scanned and a computer algorithm quantified the area of CD20 stained B-cells as a measure of B cell density within the outlined regions of prostate cancer (intra-tumoral region), versus extra-tumoral prostate tissue. Correlations were analyzed between B-cell density and demographic and clinical variables, including D'Amico risk groups and disease recurrence. Results: For the entire cohort, the mean intra-tumoral B cell density was higher (3.22 SE = 0.29) than in the extra-tumoral region of each prostatectomy section (2.24, SE = 0.19) (paired t test; P < 0.001). When analyzed according to D'Amico risk group, the intra-tumoral B cell infiltration in low risk (0.0377 vs. 0.0246; p = 0.151) and intermediate risk (0.0260 vs. 0.0214; p = 0.579) patient prostatectomy specimens did not show significantly more B-cells within the PCa tumor. However, patient specimens from the high-risk group (0.0301 vs. 0.0197; p < 0.001) and from those who eventually had PCa recurrence or progression (0.0343 vs. 0.0246; p = 0.019) did show significantly more intra-tumoral CD20+ B-cell staining. Extent of B-cell infiltration in the prostatectomy specimens did not correlate with any other clinical parameters. Conclusions: Our study shows that higher B-cell infiltration was present within the intra-tumoral PCa regions compared to the extra-tumoral benign prostate tissue regions in prostatectomy sections. For this study we developed a new method to measure B-cells using computer-assisted digitized image analysis. Accurate, consistent quantitation of B-cells in prostatectomy specimens is essential for future clinical trials evaluating the effect of B cell ablating antibodies. The interaction of B-cells and PCa may serve as the basis for new therapeutic targets.

Original languageEnglish (US)
Article number30
JournalJournal of Translational Medicine
Volume12
Issue number1
DOIs
StatePublished - Jan 30 2014

    Fingerprint

Keywords

  • B-cells
  • CD20
  • CRPC: castrate-resistant prostate cancer
  • D'Amico risk stratification
  • Digital IHC image analysis
  • Immunohistochemistry
  • Prostatectomy
  • TIL: tumor infiltrating lymphocyte

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Woo, J. R., Liss, M. A., Muldong, M. T., Palazzi, K., Strasner, A., Ammirante, M., Varki, N., Shabaik, A., Howell, S., Kane, C. J., Karin, M., & Jamieson, C. A. M. (2014). Tumor infiltrating B-cells are increased in prostate cancer tissue. Journal of Translational Medicine, 12(1), [30]. https://doi.org/10.1186/1479-5876-12-30