BACKGROUND The SPINK1 molecular subtype is more common in African-American (AA) men with prostatic adenocarcinoma (PCa) than European Americans (EA). Studies have suggested that SPINK1 expression is associated with more aggressive disease. However, the size, follow-up, and racial diversity of prior patient cohorts have limited our understanding of SPINK1 expression in AA men. The objective was to determine the associations between SPINK1 subtype, race, and oncologic outcomes after radical prostatectomy (RP). METHODS A total of 186 AA and 206 EA men who underwent RP were matched according to pathologic grade. We examined SPINK1 status by immunohistochemistry on tissue microarrays using a genetically validated assay. Cox proportional hazard analyses assessed the association of SPINK1 status with oncologic outcomes in race-specific multivariate models. A second objective was to determine the correlation between CD3/CD8 T cell densities with SPINK1 status and race, using immunostaining and automated image analysis. RESULTS SPINK1-positive subtype was present in 25% (45/186) of AA and 15% (30/206) of EA men (p = 0.013). There were no differences in pathologic grade, pathologic stage, biochemical recurrence (BCR)-free survival, or metastasis-free survival between SPINK1-positive and SPINK1-negative tumors in the overall cohort or by race. In multivariate analyses, SPINK1 expression was not associated with BCR (AA: HR 0.99, 95% CI 0.56-1.75, p = 0.976; EA: HR 0.88, 95% CI 0.43-1.77, p = 0.720) or metastasis (AA: HR 0.79, 95% CI 0.25-2.49, p = 0.691; EA: HR 1.55, 95% CI 0.58-4.11, p = 0.381) in either AA or EA men. There were no significant differences in surrounding CD3/CD8 lymphocyte densities between SPINK1-positive and SPINK1-negative tumors in either race. CONCLUSIONS SPINK1-positive subtype is more prevalent in AA than EA men with PCa. Contrary to previous studies, we found that SPINK1 protein expression was not associated with worse pathologic or oncologic outcomes after RP in either AA men or EA men.

中文翻译：

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SPINK1 表达在非裔美国人前列腺癌中富集，但与前列腺切除术后免疫浸润或肿瘤学结果的改变无关。

背景 SPINK1 分子亚型在患有前列腺腺癌 (PCa) 的非裔美国人 (AA) 男性中比欧洲裔美国人 (EA) 更常见。研究表明，SPINK1 表达与更具侵袭性的疾病有关。然而，先前患者队列的规模、随访和种族多样性限制了我们对 AA 男性中 SPINK1 表达的理解。目的是确定 SPINK1 亚型、种族和根治性前列腺切除术 (RP) 后肿瘤学结果之间的关联。方法 186 名 AA 和 206 名接受 RP 的 EA 男性根据病理分级进行匹配。我们使用经过基因验证的测定法通过组织微阵列上的免疫组织化学检查了 SPINK1 状态。Cox 比例风险分析评估了种族特异性多变量模型中 SPINK1 状态与肿瘤学结果的关联。第二个目标是使用免疫染色和自动图像分析来确定 CD3/CD8 T 细胞密度与 SPINK1 状态和种族之间的相关性。结果 SPINK1 阳性亚型存在于 25% (45/186) 的 AA 和 15% (30/206) 的 EA 男性中 (p = 0.013)。在整个队列或种族中，SPINK1 阳性和 SPINK1 阴性肿瘤的病理分级、病理分期、无生化复发 (BCR) 生存期或无转移生存期没有差异。在多变量分析中，SPINK1 表达与 BCR（AA：HR 0.99，95% CI 0.56-1.75，p = 0.976；EA：HR 0.88，95% CI 0.43-1.77，p = 0.720）或转移（AA：HR）无关0.79，95% CI 0.25-2.49，p = 0.691；EA：HR 1.55，95% CI 0.58-4.11, p = 0.381) 在 AA 或 EA 男性中。在两个种族中，SPINK1 阳性和 SPINK1 阴性肿瘤的周围 CD3/CD8 淋巴细胞密度没有显着差异。结论 SPINK1 阳性亚型在 AA 中比患有 PCa 的 EA 男性更普遍。与之前的研究相反，我们发现 SPINK1 蛋白表达与 AA 男性或 EA 男性 RP 后更差的病理或肿瘤学结果无关。