Brandi Franziska, Grupp Katharina, Hube-Magg Claudia, Kluth Martina, Lang Dagmar, Minner Sarah, Möller-Koop Christina, Graefen Markus, Heinzer Hans, Tsourlakis Maria Christina, Wittmer Corinna, Jacobsen Frank, Huland Hartwig, Steurer Stefan, Lebok Patrick, Hinsch Andrea, Wilczak Waldemar, Schlomm Thorsten, Simon Ronald
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg D-20246, Germany.
General, Visceral and Thoracic Surgery Department and Clinic, University Medical Center Hamburg-Eppendorf, Hamburg D-20246, Germany.
Oncol Lett. 2018 Nov;16(5):6238-6244. doi: 10.3892/ol.2018.9417. Epub 2018 Sep 7.
Approximately 50% of prostate cancer types harbor the transmembrane protease, serine 2: Erythroblast transformation-specific-related gene (ERG) fusion, resulting in oncogenic expression of the ERG transcription factor. ERG represents an attractive target for potential future anticancer therapy in advanced and metastatic prostate cancer. To better understand whether the analysis of the primary cancer is sufficient to estimate the ERG expression status of the lymph node metastases, the present study examined patterns of immunohistochemical ERG expression in a tissue microarray created from multiple primary and metastatic sites of 77 prostate cancer tissues. Among the identified tumor types, 80% were either entirely ERG-positive (38%) or ERG-negative (42%) across all (at least 9) analyzed different tumor sites. The results were heterogeneous in 20% of the tumor types and typically resulted from small ERG-negative areas within otherwise ERG-positive tumor types. Comparison of the ERG expression status in 51 primary cancer types with at least three interpretable lymph node metastases revealed an entirely identical ERG status in all tumor sites in 75% of the cases, including 16 ERG-positive and 22 ERG-negative cancer types. The remaining 13 cancer types exhibited ERG heterogeneity within the primary tumor, while all metastases had an identical (12 positive and 1 negative) ERG status. The results of the present study revealed a high degree of concordance of the ERG expression status between primary prostate cancer types and their lymph node metastases. Therefore, potential anti-ERG therapy may also be effective against lymph node metastases in the majority of cases of ERG-positive metastatic prostate cancer.
大约50%的前列腺癌类型存在跨膜蛋白酶丝氨酸2:成红细胞转化特异性相关基因(ERG)融合,导致ERG转录因子的致癌性表达。ERG是晚期和转移性前列腺癌未来潜在抗癌治疗的一个有吸引力的靶点。为了更好地了解原发性癌的分析是否足以估计淋巴结转移灶的ERG表达状态,本研究在一个由77个前列腺癌组织的多个原发性和转移部位构建的组织芯片中检测了ERG免疫组化表达模式。在已确定的肿瘤类型中,80%在所有(至少9个)分析的不同肿瘤部位要么完全ERG阳性(38%),要么ERG阴性(42%)。20%的肿瘤类型结果存在异质性,通常是由于在其他ERG阳性肿瘤类型中有小的ERG阴性区域。对51种原发性癌类型及其至少三个可解释的淋巴结转移灶的ERG表达状态进行比较,结果显示75%的病例在所有肿瘤部位的ERG状态完全相同,包括16种ERG阳性和22种ERG阴性癌类型。其余13种癌类型在原发性肿瘤内表现出ERG异质性,而所有转移灶具有相同的(12个阳性和1个阴性)ERG状态。本研究结果显示原发性前列腺癌类型与其淋巴结转移灶之间的ERG表达状态高度一致。因此,在大多数ERG阳性转移性前列腺癌病例中,潜在的抗ERG治疗可能对淋巴结转移也有效。