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Clonal evaluation of prostate cancer molecular heterogeneity in biopsy samples by dual immunohistochemistry and dual RNA in situ hybridization.
Modern Pathology ( IF 7.1 ) Pub Date : 2020-04-01 , DOI: 10.1038/s41379-020-0525-0 Pavithra Dedigama-Arachchige 1 , Shannon Carskadon 1 , Jia Li 2 , Ian Loveless 2 , Mohamed Alhamar 3 , James O Peabody 1 , Hans Stricker 1 , Dhananjay A Chitale 3 , Craig G Rogers 1 , Mani Menon 1 , Nilesh S Gupta 3 , Tarek A Bismar 4 , Sean R Williamson 3 , Nallasivam Palanisamy 1
Modern Pathology ( IF 7.1 ) Pub Date : 2020-04-01 , DOI: 10.1038/s41379-020-0525-0 Pavithra Dedigama-Arachchige 1 , Shannon Carskadon 1 , Jia Li 2 , Ian Loveless 2 , Mohamed Alhamar 3 , James O Peabody 1 , Hans Stricker 1 , Dhananjay A Chitale 3 , Craig G Rogers 1 , Mani Menon 1 , Nilesh S Gupta 3 , Tarek A Bismar 4 , Sean R Williamson 3 , Nallasivam Palanisamy 1
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Prostate cancer is frequently multifocal. Although there may be morphological variation, the genetic underpinnings of each tumor are not clearly understood. To assess the inter and intra tumor molecular heterogeneity in prostate biopsy samples, we developed a combined immunohistochemistry and RNA in situ hybridization method for the simultaneous evaluation of ERG, SPINK1, ETV1, and ETV4. Screening of 601 biopsy cores from 120 consecutive patients revealed multiple alterations in a mutually exclusive manner in 37% of patients, suggesting multifocal tumors with considerable genetic differences. Furthermore, the incidence of molecular heterogeneity was higher in African Americans patients compared with Caucasian American patients. About 47% of the biopsy cores with discontinuous tumor foci showed clonal differences with distinct molecular aberrations. ERG positivity occurred in low-grade cancer, whereas ETV4 expression was observed mostly in high-grade cancer. Further studies revealed correlation between the incidence of molecular markers and clinical and pathologic findings, suggesting potential implications for diagnostic pathology practice, such as defining dominant tumor nodules and discriminating juxtaposed but molecularly different tumors of different grade patterns.
中文翻译：
通过双重免疫组织化学和双重 RNA 原位杂交对活检样本中前列腺癌分子异质性的克隆评估。
前列腺癌通常是多灶性的。尽管可能存在形态学变异，但每种肿瘤的遗传基础尚不清楚。为了评估前列腺活检样本中肿瘤间和肿瘤内的分子异质性，我们开发了一种联合免疫组织化学和 RNA 原位杂交方法，用于同时评估 ERG、SPINK1、ETV1 和 ETV4。对来自 120 名连续患者的 601 个活检核心进行的筛查显示，37% 的患者以相互排斥的方式存在多种改变，这表明多灶性肿瘤具有相当大的遗传差异。此外，与美国白人患者相比，非裔美国人患者的分子异质性发生率更高。约 47% 的具有不连续肿瘤病灶的活检核心显示具有明显分子畸变的克隆差异。ERG 阳性发生在低级别癌症中，而 ETV4 表达主要出现在高级癌症中。进一步的研究揭示了分子标志物的发生率与临床和病理学发现之间的相关性，表明对诊断病理学实践的潜在影响，例如定义显性肿瘤结节和区分并列但分子不同的不同分级模式的肿瘤。
更新日期：2020-04-24
中文翻译：
通过双重免疫组织化学和双重 RNA 原位杂交对活检样本中前列腺癌分子异质性的克隆评估。
前列腺癌通常是多灶性的。尽管可能存在形态学变异，但每种肿瘤的遗传基础尚不清楚。为了评估前列腺活检样本中肿瘤间和肿瘤内的分子异质性，我们开发了一种联合免疫组织化学和 RNA 原位杂交方法，用于同时评估 ERG、SPINK1、ETV1 和 ETV4。对来自 120 名连续患者的 601 个活检核心进行的筛查显示，37% 的患者以相互排斥的方式存在多种改变，这表明多灶性肿瘤具有相当大的遗传差异。此外，与美国白人患者相比，非裔美国人患者的分子异质性发生率更高。约 47% 的具有不连续肿瘤病灶的活检核心显示具有明显分子畸变的克隆差异。ERG 阳性发生在低级别癌症中，而 ETV4 表达主要出现在高级癌症中。进一步的研究揭示了分子标志物的发生率与临床和病理学发现之间的相关性，表明对诊断病理学实践的潜在影响，例如定义显性肿瘤结节和区分并列但分子不同的不同分级模式的肿瘤。
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