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Abstract：
Approximately 30% of seminoma (SEM) patients present with moderately elevated human chorionic gonadotropin (hCG) levels at first diagnosis. In case of high hCG serum levels, the presence of a non-SEM component, i.e. choriocarcinoma (CC), may be assumed. To characterize cases described as pure seminoma with high serum hCG levels, tissue samples and DNA were analyzed. Patient files from an international registry were screened for patients with SEM and extraordinarily high hCG serum levels. IHC and qRT-PCR analysis was performed for markers of SEM, embryonal carcinoma (EC) and CC/trophoblast cells. The cell lines TCam-2 (SEM), 2102EP, NCCIT, NT2/D1 (EC) and JAR, JEG3 and BeWo (CC) were included for comparison. Of 1031 SEM patients screened, 39 patients (3.7%) showed hCG serum levels > 1000 U/l. Of these, tumor material for IHC and RNA for qRT-PCR was available from n = 7 patients and n = 3 patients, respectively. Median pre-orchiectomy serum hCG level was 5356 U/l (range: 1224-40909 U/L). Histopathologically, all investigated samples were classified as SEM with syncytiotrophoblast sub-populations. SEM cells were SALL4+ / OCT3/4+ / D2-40+, while syncytiotrophoblast cells were hCG+ / GATA3+ / p63+ and SOX2-/CDX2-. qRT-PCR analysis detected trophoblast stem cell markers CDX2, EOMES and TFAP2C as well as the trophectoderm-specifier TEAD4, but not GATA3. Additionally, SOX17 and PRAME, but not SOX2, were detected, confirming the pure SEM-like gene expression signature of the analyzed samples. In conclusion, excessively increased hCG serum levels can appear in patients with pure SEM. To explain detectable hCG serum levels, it is important to diagnose the subtype of a SEM with syncytiotrophoblasts.
摘要：
大约30％的精原细胞瘤（SEM）患者在首次诊断时表现出中度升高的人绒毛膜促性腺激素（hCG）水平。在高hCG血清水平的情况下，存在非SEM成分，即绒毛膜癌(CC)，可以假设。描述为高血清hCG水平的纯精原细胞瘤的病例，分析组织样本和DNA。从国际注册中心的患者档案中筛选出具有SEM和极高的hCG血清水平的患者。对SEM标记物进行IHC和qRT-PCR分析，胚胎癌（EC）和CC/滋养层细胞。细胞系TCam-2(SEM),2102EP,NCCIT,NT2/D1（EC）和JAR，包括JEG3和BeWo(CC)用于比较。在筛查的1031名SEM患者中，39例患者(3.7%)显示hCG血清水平>1000U/l。其中,用于IHC的肿瘤材料和用于qRT-PCR的RNA可从n=7患者和n=3患者获得，分别。睾丸切除术前血清hCG水平中位数为5356U/l（范围：1224-40909U/L）。组织病理学,所有调查样本均被分类为具有合胞体滋养层亚群的SEM.SEM细胞为SALL4+/OCT3/4+/D2-40+，合胞体滋养层细胞为hCG+/GATA3+/p63+和SOX2-/CDX2-。qRT-PCR分析检测到滋养层干细胞标志物CDX2，EOMES和TFAP2C以及滋养外胚层说明符TEAD4，但未检测到GATA3。此外,SOX17和PRAME,但不是SOX2，被检测到，确认分析样品的纯SEM样基因表达特征。总之,单纯SEM患者可出现血清hCG水平过度升高。为了解释可检测的hCG血清水平，诊断具有合胞体滋养层的SEM亚型很重要。
