Dysregulation of S100A8 is described in many different human tumor types, but its role in prostate cancer is unknown. To evaluate the clinical relevance of S100A8 expression in prostate cancer, a tissue microarray containing 13,665 tumors was analyzed by immunohistochemistry. Cytoplasmic S100A8 staining was compared to prostate cancer phenotype, patient prognosis and molecular features including TMPRSS2:ERG fusion status and deletions of PTEN, 3p, 5q and 6q. S100A8 immunostaining was typically seen in normal prostate tissue but lost in 60% of 9786 interpretable prostate cancers. In the remaining tumors, S100A8 was considered weak in 17.9%, moderate in 17.8% and strong in 5.4% of cases. Loss of S100A8 expression was linked to advanced tumor stage, high Gleason grade, positive nodal status, positive surgical margin and high preoperative PSA (P < .0001 each). In addition, loss of S100A8 expression was associated with TMPRSS2:ERG fusions (P < .0001), deletions of PTEN, 3p, and 6q (P < .005), and a high number of genomic deletions per tumor (P = .0009). Absence of S100A8 immunostaining was also linked to an elevated risk for early PSA recurrence (P < .0001). In a multivariate analysis limited to features that are preoperatively available, the prognostic impact of S100A8 expression (P < .0001) was independent of clinical stage, Gleason grade, and serum PSA level (P < .0001). Taken together, the results of our study demonstrate that complete loss of S100A8 expression is linked to adverse tumor features and predicts early biochemical recurrence in prostate cancer. S100A8 measurement, either alone or in combination might be of clinical utility in prostate cancers.

在许多不同的人类肿瘤类型中都描述了S100A8的失调，但尚不清楚它在前列腺癌中的作用。为了评估S100A8表达在前列腺癌中的临床相关性，通过免疫组织化学分析了包含13,665个肿瘤的组织微阵列。将细胞质S100A8染色与前列腺癌表型，患者预后以及包括TMPRSS2：ERG融合状态和PTEN缺失在内的分子特征进行了比较，3p，5q和6q。S100A8免疫染色通常见于正常前列腺组织，但在9786个可解释的前列腺癌中有60％消失。在其余的肿瘤中，S100A8被认为弱17.9％，中度17.8％，强5.4％。S100A8表达的丧失与肿瘤晚期，格里森评分高，淋巴结阳性，手术切缘阳性和术前PSA高有关（ 每个P <.0001）。此外，S100A8表达的丧失与TMPRSS2：ERG融合（P <.0001），PTEN，3p和6q的缺失（P  <.005）以及每个肿瘤的大量基因组缺失有关（P  = .0009 ）。缺乏S100A8免疫染色也与PSA早期复发的风险增加有关（P  <.0001）。在仅限于术前可用特征的多元分析中，S100A8表达的预后影响（P  <.0001）与临床阶段，格里森分级和血清PSA水平无关（P <.0001）。两者合计，我们的研究结果表明S100A8表达的完全丧失与不良的肿瘤特征有关，并预测前列腺癌的早期生化复发。单独或组合使用S100A8测量可能在前列腺癌中具有临床效用。