Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
Neoplasia. 2019 Sep;21(9):872-881. doi: 10.1016/j.neo.2019.07.003. Epub 2019 Aug 2.
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.
S100A8 的失调在许多不同的人类肿瘤类型中都有描述，但它在前列腺癌中的作用尚不清楚。为了评估 S100A8 表达在前列腺癌中的临床相关性，我们通过免疫组织化学分析了包含 13665 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、3p、5q 和 6q 缺失在内的分子特征进行了比较。S100A8 免疫染色通常在正常前列腺组织中可见，但在 9786 例可解释的前列腺癌中有 60%丢失。在其余肿瘤中，S100A8 在 17.9%的病例中被认为弱，在 17.8%的病例中为中等，在 5.4%的病例中为强。S100A8 表达的丧失与肿瘤晚期、高 Gleason 分级、阳性淋巴结状态、阳性手术切缘和高术前 PSA 相关（P<.0001 各）。此外，S100A8 表达的丧失与 TMPRSS2:ERG 融合（P<.0001）、PTEN、3p 和 6q 的缺失（P<.005）以及肿瘤中每例的基因组缺失数量增加相关（P=0.0009）。S100A8 免疫染色的缺失也与早期 PSA 复发的风险增加相关（P<.0001）。在仅限于术前可获得的特征的多变量分析中，S100A8 表达的预后影响（P<.0001）独立于临床分期、Gleason 分级和血清 PSA 水平（P<.0001）。总之，我们的研究结果表明，S100A8 表达完全缺失与不良肿瘤特征相关，并预测前列腺癌的早期生化复发。S100A8 的测量，无论是单独使用还是组合使用，在前列腺癌中可能具有临床实用性。
