Tumor infiltrating B-cells are increased in prostate cancer tissue.
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.
Jason R
JR
Woo
Michael A
MA
Liss
Michelle T
MT
Muldong
Kerrin
K
Palazzi
Amy
A
Strasner
Massimo
M
Ammirante
Nissi
N
Varki
Ahmed
A
Shabaik
Stephen
S
Howell
Christopher J
CJ
Kane
Michael
M
Karin
Department of Urology and Department of Surgery, University of California San Diego, La Jolla, CA, USA. camjamieson@ucsd.edu.
Christina A M
CA
Jamieson
D000818:Animals; D018951:Antigens, CD20 / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology*; D002452:Cell Count; D003710:Demography; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000473:pathology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000473:pathology* / Q000601:surgery; D016896:Treatment Outcome
D018951:Antigens, CD20