Michigan Center for Translational Pathology, Ann Arbor, MI, USA.
Mod Pathol. 2013 Jun;26(6):835-48. doi: 10.1038/modpathol.2012.234. Epub 2013 Jan 25.
Identification of new molecular markers has led to the molecular classification of prostate cancer based on driving genetic lesions. The translation of these discoveries for clinical use necessitates the development of simple, reliable and rapid detection systems to screen patients for specific molecular aberrations. We developed two dual-color immunohistochemistry-based assays for the simultaneous assessment of ERG-PTEN and ERG-SPINK1 in prostate cancer. A total of 232 cases from 184 localized and 48 metastatic prostate cancers were evaluated for ERG-PTEN and 284 cases from 228 localized and 56 metastatic prostate cancers were evaluated for ERG-SPINK1. Of the 232 cases evaluated for ERG-PTEN, 81 (35%) ERG-positive and 77 (33%) PTEN-deleted cases were identified. Of the 81 ERG-positive cases, PTEN loss was confirmed in 35 (15%) cases by fluorescence in situ hybridization (FISH). PTEN status was concordant in 203 cases (sensitivity 90% and specificity 87%; P<0.0001) by both immunohistochemisty and FISH; however, immunohistochemisty could not distinguish between heterozygous and homozygous deletion status of PTEN. Of the 284 cases evaluated for ERG-SPINK1, 111 (39%) cases were positive for ERG. In the remaining 173 ERG-negative cases, SPINK1 was positive in 26 (9%) cases. SPINK1 expression was found to be mutually exclusive with ERG expression; however, we identified two cases, of which one showed concomitant expression of ERG and SPINK1 in the same tumor foci, and in the second case ERG and SPINK1 were seen in two independent foci of the same tumor nodule. Unlike the homogenous ERG staining in cancer tissues, heterogeneous SPINK1 staining was observed in the majority of the cases. Further studies are required to understand the molecular heterogeneity of cases with concomitant ERG-SPINK1 expression. Automated dual ERG-PTEN and ERG-SPINK1 immunohistochemisty assays are simple, reliable and portable across study sites for the simultaneous assessment of these proteins in prostate cancer.
新的分子标记物的鉴定导致了基于驱动遗传病变的前列腺癌的分子分类。为了将这些发现转化为临床应用，需要开发简单、可靠和快速的检测系统，以筛选出具有特定分子异常的患者。我们开发了两种基于双重免疫组织化学的检测方法，用于同时评估前列腺癌中的 ERG-PTEN 和 ERG-SPINK1。总共评估了 184 例局限性和 48 例转移性前列腺癌中的 232 例用于 ERG-PTEN，以及 228 例局限性和 56 例转移性前列腺癌中的 284 例用于 ERG-SPINK1。在评估的 232 例 ERG-PTEN 中，发现 81 例（35%）为 ERG 阳性和 77 例（33%）PTEN 缺失。在 81 例 ERG 阳性病例中，通过荧光原位杂交（FISH）证实 35 例（15%）存在 PTEN 缺失。通过免疫组织化学和 FISH 两种方法，PTEN 状态在 203 例中是一致的（敏感性 90%，特异性 87%；P<0.0001）；然而，免疫组织化学无法区分 PTEN 的杂合和纯合缺失状态。在评估的 284 例 ERG-SPINK1 中，111 例（39%）为 ERG 阳性。在其余 173 例 ERG 阴性病例中，26 例（9%）SPINK1 阳性。SPINK1 表达与 ERG 表达相互排斥；然而，我们发现了两例，其中一例在同一肿瘤病灶中同时表达 ERG 和 SPINK1，在第二例中，ERG 和 SPINK1 出现在同一肿瘤结节的两个独立病灶中。与癌组织中均匀的 ERG 染色不同，大多数病例中观察到不均匀的 SPINK1 染色。需要进一步研究来了解同时具有 ERG-SPINK1 表达的病例的分子异质性。自动化的双重 ERG-PTEN 和 ERG-SPINK1 免疫组织化学检测方法简单、可靠，在研究现场之间可移植，可用于同时评估前列腺癌中的这些蛋白。
