Department of Endocrinology and Neuroendocrine Tumors, Medical University of Silesia, ul. Ceglana 35, 40-514, Katowice, Poland.
Department of Gastrointestinal Surgery, Medical University of Silesia, ul. Medykow 14, 40-752, Katowice, Poland.
BMC Gastroenterol. 2020 Jul 23;20(1):235. doi: 10.1186/s12876-020-01348-2.
NETest, a novel multi-gene liquid biopsy has utility in neuroendocrine tumor (NET) diagnosis and identification of residual disease. We independently assessed utility of the NETest to diagnose gastric neuroendocrine neoplasms (GNENs) and identify micro- and macroscopic residual disease.
Cohorts comprised histologically confirmed GNENs at biopsy, n = 46; GNETs Type 1: 42 (32 NET G1, 10 NET G2), a GNET Type 3: 1 well-differentiated NET G3, neuroendocrine carcinomas (NECs) (n = 3), and controls (n = 63). Disease status at sampling was assessed by gastroscopy, histology (resection margin [R] positivity of polypectomy or biopsy), EUS, CT or MRI, and/or Ga-DOTA-TATE PET/CT. Groups included image- (gastroscopy, EUS, and anatomical and/or functional imaging) positive or image negative disease. NETest assay by PCR (spotted plates, normal cut-off: 20).
mean ± SD.
Disease extent: Image-negative (n = 30) (21 R0, 9 R1); Image-positive, n = 16.
NETest was increased in GNETs (23 ± 11) vs. controls (7 ± 4, p < 0.0001). In histology-positive, the NETest accuracy was 100% (25/25). Microscopic disease: In image-negative but R1, NETest was elevated in 100% (9/9; 28 ± 9). Levels were elevated vs. controls (7 ± 4, p < 0.0001), or R0 (16 ± 11, p = 0.02). Eight of 21 R0, exhibited positive NETest. Macroscopic disease: Gastric lesions were multiple: 38%, single: 62%, submucosal: 13%, or ulcerated: 13%. Lesions size was ≤5 mm (50%), > 5-9.9 mm (17%), 10-19.9 mm (17%), ≥20 mm (17%) [≥10 mm: 34%). The NETest accuracy was 100% (16/16). Levels (28 ± 7) were higher than controls (7 ± 4, p < 0.0001) or R0 (16 ± 11, p = 0.002) but not to R1 (28 ± 9, p = 0.5).
NETest is diagnostic for gastric NETs. Elevated levels identify both microscopic and macroscopic residual disease. In histology/image-negative disease, elevated NETest may reflect early evidence of increased neuroendocrine gene expression of hypergastrinemia-induced neoplastic transformation of enterochromaffin-like (ECL) cells to tumor status. A sensitive liquid biopsy has utility in the management and surveillance of gastric NET disease.
NETest 是一种新型的多基因液体活检，在神经内分泌肿瘤 (NET) 的诊断和残留疾病的鉴定方面具有应用价值。我们独立评估了 NETest 用于诊断胃神经内分泌肿瘤 (GNENs) 和识别微残留病和宏观残留病的效用。
本研究包括经组织学证实的活检 GNENs 患者，共 46 例；GNET 1 型：42 例（32 例 NET G1，10 例 NET G2），GNET 3 型：1 例分化良好的 NET G3，神经内分泌癌 (NEC)（n=3），对照组（n=63）。采样时的疾病状态通过胃镜检查、组织学（息肉切除术或活检的切缘 [R] 阳性）、EUS、CT 或 MRI 和/或 Ga-DOTA-TATE PET/CT 评估。分为影像学阳性（胃镜、EUS、解剖和/或功能影像学）或影像学阴性疾病。NETest 检测采用 PCR（斑点板，正常截断值：20）。
平均值±标准差。
疾病范围：影像学阴性（n=30）（21 例 R0，9 例 R1）；影像学阳性，n=16。
GNETs 中 NETest 升高（23±11）vs. 对照组（7±4，p<0.0001）。在组织学阳性患者中，NETest 的准确率为 100%（25/25）。微残留病：在影像学阴性但 R1 的患者中，NETest 升高 100%（9/9；28±9）。与对照组（7±4，p<0.0001）或 R0（16±11，p=0.02）相比，水平升高。21 例 R0 中有 8 例显示阳性 NETest。大残留病：胃病变为多发：38%，单发：62%，黏膜下：13%，或溃疡：13%。病变大小≤5mm（50%）、>5-9.9mm（17%）、10-19.9mm（17%）、≥20mm（17%）[≥10mm：34%）。NETest 的准确率为 100%（16/16）。水平（28±7）高于对照组（7±4，p<0.0001）或 R0（16±11，p=0.002），但低于 R1（28±9，p=0.5）。
NETest 可用于诊断胃 NETs。升高的水平可识别微残留病和大残留病。在组织学/影像学阴性疾病中，升高的 NETest 可能反映了胃泌素诱导的 ECL 细胞向肿瘤状态的肿瘤性转化导致的神经内分泌基因表达增加的早期证据。一种敏感的液体活检在胃 NET 疾病的管理和监测中有应用价值。
