Robert Wood Johnson Clinical Scholars Program, Yale University School of Medicine, New Haven, Connecticut, USA.
Clin Cancer Res. 2009 Dec 1;15(23):7316-21. doi: 10.1158/1078-0432.CCR-09-1263. Epub 2009 Nov 24.
We assessed the association of quantitative clinical and pathologic information, including serum and tissue pro-prostate-specific antigen (proPSA) measurements, with outcomes among men with prostate cancer in an expectant management (active surveillance) program.
We identified 71 men enrolled in expectant management with frozen serum and tissue available from diagnosis: 39 subsequently developed unfavorable biopsies (Gleason score > or =7, > or =3 cores positive for cancer, >50% of any core involved with cancer), whereas 32 maintained favorable biopsies (median follow-up, 3.93 years). Serum total PSA, free PSA (fPSA), and [-2]proPSA were measured by the Beckman Coulter immunoassay. [-5/-7]proPSA was evaluated in cancer and benign-adjacent areas (BAA) by quantitative immunohistochemistry. Cox proportional hazards and Kaplan-Meier analyses were used to identify significant associations with unfavorable biopsy conversion.
The ratio [-2]proPSA/% fPSA in serum was significantly higher at diagnosis (0.87 +/- 0.44 versus 0.65 +/- 0.36 pg/mL; P = 0.02) in men developing unfavorable biopsies. [-5/-7]proPSA tissue staining was more intense (4104.09 +/- 3033.50 versus 2418.06 +/- 1606.04; P = 0.03) and comprised a greater fractional area (11.58 +/- 7.08% versus 6.88 +/- 5.20%; P = 0.01) in BAA of these men. Serum [-2]proPSA/% fPSA [hazard ratio, 2.53 (1.18-5.41); P = 0.02], BAA [-5/-7]proPSA % area [hazard ratio, 1.06 (1.01-1.12); P = 0.02] and BAA [-5/-7]proPSA stain intensity [hazard ratio, 1.000213 (1.000071-1.000354); P = 0.003] were significantly associated with unfavorable biopsy in Kaplan-Meier and Cox analyses. Serum [-2]proPSA/% fPSA significantly correlated with BAA [-5/-7]proPSA % area (rho = 0.40; P = 0.002) and BAA [-5/-7]proPSA stain intensity (rho = 0.33; P = 0.016).
In a prospective cohort of men enrolled into expectant management for prostate cancer, serum and tissue levels of proPSA at diagnosis are associated with need for subsequent treatment. The increase in serum proPSA/% fPSA might be driven by increased proPSA production from "premalignant" cells in the prostate BAA.
我们评估了定量临床和病理信息，包括血清和组织原前列腺特异性抗原（proPSA）测量值，与前列腺癌患者在期待管理（主动监测）计划中的结局之间的关联。
我们确定了 71 名接受期待管理的男性，其冷冻血清和组织可从诊断时获得：39 名男性随后发展为不良活检（Gleason 评分≥7、≥3 个核心阳性癌症、≥50%的任何核心与癌症有关），而 32 名男性保持良好的活检（中位随访 3.93 年）。血清总 PSA、游离 PSA（fPSA）和 [-2]proPSA 通过贝克曼库尔特免疫测定法进行测量。[-5/-7]proPSA 通过定量免疫组织化学在癌症和良性相邻区域（BAA）进行评估。Cox 比例风险和 Kaplan-Meier 分析用于确定与不良活检转换相关的显著关联。
在发展为不良活检的男性中，血清中 [-2]proPSA/%fPSA 的比值在诊断时明显更高（0.87 +/- 0.44 与 0.65 +/- 0.36 pg/mL；P = 0.02）。这些男性的 BAA 中 [-5/-7]proPSA 组织染色强度更高（4104.09 +/- 3033.50 与 2418.06 +/- 1606.04；P = 0.03），并且包含更大的分数区域（11.58 +/- 7.08% 与 6.88 +/- 5.20%；P = 0.01）。血清 [-2]proPSA/%fPSA [危险比，2.53（1.18-5.41）；P = 0.02]、BAA [-5/-7]proPSA%面积 [危险比，1.06（1.01-1.12）；P = 0.02]和 BAA [-5/-7]proPSA 染色强度 [危险比，1.000213（1.000071-1.000354）；P = 0.003]在 Kaplan-Meier 和 Cox 分析中与不良活检显著相关。血清 [-2]proPSA/%fPSA 与 BAA [-5/-7]proPSA%面积（rho = 0.40；P = 0.002）和 BAA [-5/-7]proPSA 染色强度（rho = 0.33；P = 0.016）显著相关。
在一项前瞻性队列研究中，接受前列腺癌期待管理的男性在诊断时的血清和组织 proPSA 水平与后续治疗的需求相关。血清 proPSA/%fPSA 的增加可能是由于前列腺 BAA 中“癌前”细胞的 proPSA 产生增加所致。
