Cimitan M, Buonadonna A, Cannizzaro R, Canzonieri V, Borsatti E, Ruffo R, De Apollonia L
Nuclear Medicine Unit, National Cancer Institute (CRO-IRCCS), Aviano, Italy.
Ann Oncol. 2003 Jul;14(7):1135-41. doi: 10.1093/annonc/mdg279.
Current diagnosis and staging of neuroendocrine tumors (NETs) are significantly improved by the introduction of the chromogranin A (CgA) assay in plasma or serum as a tumor marker, and by the use of somatostatin receptor scintigraphy (SRS) for tumor localization. However, the clinical role of CgA assay compared with SRS in the management of NETs has not been well elucidated.
Sixty-three consecutive patients with a histological diagnosis of NET underwent plasma CgA assay and SRS for tumor staging (23 cases), evaluation of tumor response (18 cases) and evaluation of tumor recurrence on follow-up (22 cases). Twenty-one patients had well-differentiated neuroendocrine tumors (WDNETs: 18 gastroenteropancreatic tumors and three lung NETs); 22 patients had well-differentiated neuroendocrine carcinomas (WDNECs: 17 gastroenteropancreatic carcinomas, two lung neuroendocrine carcinomas and three neuroendocrine carcinomas of unknown origin) and 20 patients had poorly differentiated neuroendocrine carcinomas (PDNECs: 14 extra-pulmonary small-cell carcinomas and six Merkel cell carcinomas). Almost all (58 of 63) NETs were non-functioning. The quantitative determination of CgA was performed in plasma using an enzyme immunoassay with a cut-off value fixed at 34 U/l. Scintigraphies with indium 111-DTPA-octreotide ((111)In-pentetreotide) included whole-body images and single photon emission computed tomography (SPECT) scans of the chest and abdomen.
SRS results were compared with CgA findings and final clinical data. The overall sensitivity of SRS and CgA, based on the final clinical data, was 77% and 55%, respectively, whereas the specificity of both SRS and CgA was 94%. Concerning tumor type, SRS accuracy was 95% for WDNETs, 86% for WDNECs and 60% for PDNECs; CgA accuracy was 76% for WDNETs, 68% for WDNECs and 50% for PDNECs. With regard to disease extent, SRS sensitivity was 100% for limited disease and 72% for advanced disease; CgA sensitivity was 43% for limited disease and 57% for advanced disease.
In our NET series, SRS proved to be more sensitive than CgA, with equivalent specificity. Tumor differentiation influences the sensitivity of SRS and CgA analysis. In addition, the plasma CgA level is related to tumor secretory activity. Nevertheless both SRS and CgA should be considered useful tools in the diagnostic work-up of NET patients.
通过将血浆或血清中的嗜铬粒蛋白A（CgA）检测作为肿瘤标志物，以及使用生长抑素受体闪烁显像（SRS）进行肿瘤定位，神经内分泌肿瘤（NETs）的当前诊断和分期有了显著改善。然而，CgA检测与SRS在NETs管理中的临床作用尚未得到充分阐明。
63例经组织学诊断为NET的连续患者接受了血浆CgA检测和SRS检查，用于肿瘤分期（23例）、评估肿瘤反应（18例）以及随访时评估肿瘤复发（22例）。21例患者患有高分化神经内分泌肿瘤（WDNETs：18例胃肠胰肿瘤和3例肺NETs）；22例患者患有高分化神经内分泌癌（WDNECs：17例胃肠胰癌、2例肺神经内分泌癌和3例来源不明的神经内分泌癌），20例患者患有低分化神经内分泌癌（PDNECs：14例肺外小细胞癌和6例默克尔细胞癌）。几乎所有（63例中的58例）NETs均为无功能型。采用酶免疫分析法在血浆中对CgA进行定量测定，临界值设定为34 U/l。使用铟111 - DTPA - 奥曲肽（（111）In - 喷替肽）进行的闪烁显像包括全身图像以及胸部和腹部的单光子发射计算机断层扫描（SPECT）。
将SRS结果与CgA结果及最终临床数据进行比较。基于最终临床数据，SRS和CgA的总体敏感性分别为77%和55%，而SRS和CgA的特异性均为94%。关于肿瘤类型，SRS对WDNETs的准确率为95%，对WDNECs为86%，对PDNECs为60%；CgA对WDNETs的准确率为76%，对WDNECs为68%，对PDNECs为50%。关于疾病范围，SRS对局限性疾病的敏感性为100%，对晚期疾病为72%；CgA对局限性疾病的敏感性为43%，对晚期疾病为57%。
在我们的NET系列研究中，SRS被证明比CgA更敏感，特异性相当。肿瘤分化程度影响SRS和CgA分析的敏感性。此外，血浆CgA水平与肿瘤分泌活性相关。尽管如此，SRS和CgA都应被视为NET患者诊断检查中的有用工具。
