Table 1_A case of de novo neuroendocrine prostate cancer presented with elevated level of serum CEA carrying BRCA2 mutation: case report and literature review.docx

BackgroundDe novo neuroendocrine prostate cancer (NEPC) is a rare subtype of prostate cancer (PCa) and few markers are available for screening and monitoring. Potential circulating or fluid markers might facilitate early diagnosis thus improving prognosis of NEPC, especially for de novo NEPC.
Case presentationA man of 71-year was presented with elevated level of serum carcinoembryonic antigen (CEA) (1296.5 ng/ml) and normal PSA (0.47ng/ml). Gastrointestinal endoscopy showed no signs of gastric or colorectal cancer. Fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) and prostate-specific membrane antigen PET-CT (PSMA PET-CT) indicated prostate cancer with metastases including pelvic lymph nodes, bone as well as lung metastases. Biopsy of prostate revealed mixed carcinoma including small cell neuroendocrine carcinoma (SCNEC) and adenocarcinoma (Gleason score of 4 + 5). Immunohistochemistry (IHC) staining and next generation sequencing demonstrated a strong expression of chromogranin A (CgA), synaptophysin (SYN) and CEA, and a germline mutation in BRCA2, respectively. After a prostatic massage, an increased level of CEA (137 ng/ml vs 5 ng/ml) was detected in urine. Olaparib, a Poly ADP-ribose polymerase inhibitor (PARPi), combined with androgen deprivation therapy (ADT) were administrated. FDG PET-CT indicated tumor regression in both quantity and size three months later, and CEA levels of serum and urine decreased to 23 ng/ml and 2.4 ng/ml 4 months later, respectively.
ConclusionThis is the first report of a de novo NEPC presented with an elevated level of CEA, in which CEA was also detected in urine specimen post a prostatic massage. After a combination treatment of ADT for 3 months, levels of CEA in both serum and urine decreased sharply when tumor regressed radiologically. CEA might be a marker of screening and monitoring of NEPC.

背景
原发性神经内分泌前列腺癌（de novo neuroendocrine prostate cancer, NEPC）是前列腺癌（prostate cancer, PCa）的罕见亚型，目前可供用于筛查与监测的标志物极少。潜在的循环或体液标志物或可助力早期诊断，从而改善NEPC患者的预后，尤其是原发性NEPC患者。

病例报告
一名71岁男性因血清癌胚抗原（carcinoembryonic antigen, CEA）水平升高（1296.5 ng/ml）且前列腺特异性抗原（prostate-specific antigen, PSA）正常（0.47ng/ml）就诊。胃肠内镜检查未发现胃或结直肠癌相关征象。氟脱氧葡萄糖正电子发射断层显像-计算机断层扫描（fluorodeoxyglucose positron emission tomography-computed tomography, FDG PET-CT）与前列腺特异性膜抗原PET-CT（prostate-specific membrane antigen PET-CT, PSMA PET-CT）提示前列腺癌伴转移，转移灶累及盆腔淋巴结、骨骼及肺部。前列腺活检结果显示为混合癌，包含小细胞神经内分泌癌（small cell neuroendocrine carcinoma, SCNEC）与腺癌（格里森评分4+5）。免疫组化（immunohistochemistry, IHC）染色与下一代测序（next generation sequencing, NGS）分别显示嗜铬粒蛋白A（chromogranin A, CgA）、突触素（synaptophysin, SYN）与CEA呈强阳性表达，且检出BRCA2胚系突变。前列腺按摩后，尿液中CEA水平升高（137 ng/ml vs 基线5 ng/ml）。予以聚ADP核糖聚合酶抑制剂（Poly ADP-ribose polymerase inhibitor, PARPi）奥拉帕利联合雄激素剥夺治疗（androgen deprivation therapy, ADT）。3个月后FDG PET-CT显示肿瘤在数量与体积上均出现退缩，4个月时血清与尿液CEA水平分别降至23 ng/ml与2.4 ng/ml。

结论
本研究首次报道了1例以CEA水平升高为表现的原发性NEPC病例，且前列腺按摩后的尿液标本中可检测到CEA。在接受该联合治疗3个月后，随着影像学证实肿瘤退缩，血清与尿液CEA水平均显著下降。CEA或可作为NEPC的筛查与监测标志物。