Evaluation of ERG and SPINK1 by Immunohistochemical Staining and Clinicopathological Outcomes in a Multi-Institutional Radical Prostatectomy Cohort of 1067 Patients.
Evaluation of ERG and SPINK1 by Immunohistochemical Staining and Clinicopathological Outcomes in a Multi-Institutional Radical Prostatectomy Cohort of 1067 Patients.
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DOI：
10.1371/journal.pone.0132343
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
McKenney JK
中科院分区：
文献类型：
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作者：
Brooks JD;Wei W;Hawley S;Auman H;Newcomb L;Boyer H;Fazli L;Simko J;Hurtado-Coll A;Troyer DA;Carroll PR;Gleave M;Lance R;Lin DW;Nelson PS;Thompson IM;True LD;Feng Z;McKenney JK
区分筛查检测出的早期前列腺癌患者和那些可以安全观察的患者已成为前列腺癌护理中的一个主要问题。前列腺癌分子亚型的鉴定为测试表征这些亚型的生物标志物是否可以用作预后的生物标志物提供了机会。由于大约 1/2 前列腺癌中编码融合转录物的 DNA 结构改变，ERG 癌蛋白的高表达以及 SPINK1 的过度表达（据称仅在 ERG 阴性肿瘤中发现）确定了两种已确定的分子亚型。我们使用由根治性前列腺切除术样本构建的多机构前列腺癌组织微阵列以及相关的详细临床数据，并严格选择复发和非复发病例，以测试 ERG 和 SPINK1 蛋白免疫组织化学染色结果的预后价值。在单变量分析中，ERG 阳性病例 (419/1067；39%) 与较低的患者年龄、术前血清 PSA 水平、较低的格里森评分 (≤3+4=7) 和改善的无复发生存期 (RFS) 相关。在多变量分析中，ERG 状态与 RFS、疾病特异性生存期 (DSS) 或总生存期 (OS) 不相关。单变量和多变量 Cox 回归分析表明，高水平 SPINK1 蛋白表达（33/1067 例；3%）与 RFS 改善相关。任一蛋白的过度表达均与临床结果无关。虽然 ERG 和 SPINK1 蛋白的表达呈负相关，但并不相互排斥，因为 3 例 (0.28%) 病例显示两者均高表达。虽然 ERG 和 SPINK1 似乎可以识别前列腺癌的离散分子亚型，但只有 SPINK1 的高表达与临床结果的改善相关。然而，就其本身而言，ERG 和 SPINK1 似乎都不是预测早期前列腺癌的有用生物标志物。
Distinguishing between patients with early stage, screen detected prostate cancer who must be treated from those that can be safely watched has become a major issue in prostate cancer care. Identification of molecular subtypes of prostate cancer has opened the opportunity for testing whether biomarkers that characterize these subtypes can be used as biomarkers of prognosis. Two established molecular subtypes are identified by high expression of the ERG oncoprotein, due to structural DNA alterations that encode for fusion transcripts in approximately ½ of prostate cancers, and over-expression of SPINK1, which is purportedly found only in ERG-negative tumors. We used a multi-institutional prostate cancer tissue microarray constructed from radical prostatectomy samples with associated detailed clinical data and with rigorous selection of recurrent and non-recurrent cases to test the prognostic value of immunohistochemistry staining results for the ERG and SPINK1 proteins. In univariate analysis, ERG positive cases (419/1067; 39%) were associated with lower patient age, pre-operative serum PSA levels, lower Gleason scores (≤3+4=7) and improved recurrence free survival (RFS). On multivariate analysis, ERG status was not correlated with RFS, disease specific survival (DSS) or overall survival (OS). High-level SPINK1 protein expression (33/1067 cases; 3%) was associated with improved RFS on univariate and multivariate Cox regression analysis. Over-expression of either protein was not associated with clinical outcome. While expression of ERG and SPINK1 proteins was inversely correlated, it was not mutually exclusive since 3 (0.28%) cases showed high expression of both. While ERG and SPINK1 appear to identify discrete molecular subtypes of prostate cancer, only high expression of SPINK1 was associated with improved clinical outcome. However, by themselves, neither ERG nor SPINK1 appear to be useful biomarkers for prognostication of early stage prostate cancer.