Department of Urology and Department of Surgery, University of California San Diego, La Jolla, CA, USA.
J Transl Med. 2014 Jan 30;12:30. doi: 10.1186/1479-5876-12-30.
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.
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.
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.
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.
在小鼠前列腺癌中观察到 B 细胞肿瘤浸润淋巴细胞（TILs）增多，但在人类前列腺癌中尚未完全记录。因此，我们利用定量计算方法研究了人类前列腺癌中浸润 B 细胞的密度。
从 53 名具有已知临床结局和 D'Amico 风险类别的根治性前列腺切除术标本中获得存档标本，并使用 B 细胞标志物 CD20 进行免疫组织化学（IHC）染色。由泌尿生殖病理学家对前列腺癌的肿瘤区域进行审阅。幻灯片被数字化扫描，计算机算法定量测定 CD20 染色 B 细胞的面积作为前列腺癌（肿瘤内区域）内 B 细胞密度的指标，与前列腺癌切除部分的非肿瘤前列腺组织进行比较。分析了 B 细胞密度与人口统计学和临床变量之间的相关性，包括 D'Amico 风险组和疾病复发。
对于整个队列，肿瘤内 B 细胞的平均密度较高（3.22 SE = 0.29），高于每个前列腺切除术切片的肿瘤外区域（2.24，SE = 0.19）（配对 t 检验；P < 0.001）。根据 D'Amico 风险组进行分析时，低危（0.0377 比 0.0246；p = 0.151）和中危（0.0260 比 0.0214；p = 0.579）患者前列腺切除标本中的肿瘤内 B 细胞浸润并没有显示出肿瘤内的 B 细胞显著增加。然而，高危组（0.0301 比 0.0197；p < 0.001）和最终发生前列腺癌复发或进展的患者（0.0343 比 0.0246；p = 0.019）的标本中显示出肿瘤内 CD20+B 细胞染色明显增多。前列腺切除术标本中 B 细胞浸润的程度与其他任何临床参数均无相关性。
我们的研究表明，与前列腺切除标本中肿瘤外良性前列腺组织区域相比，肿瘤内前列腺癌区域内存在更高的 B 细胞浸润。为此，我们开发了一种新的使用计算机辅助数字化图像分析来测量 B 细胞的方法。在前列腺癌切除标本中准确、一致地定量 B 细胞对于评估 B 细胞耗竭抗体效果的未来临床试验至关重要。B 细胞与前列腺癌的相互作用可能为新的治疗靶点提供依据。
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