Department of Pathology, Daping Hospital and Research Institute of Surgery, Army Military Medical University (Army Special Medical Center), Chongqing, China.
Cancer Center, Daping Hospital and Research Institute of Surgery, Army Military Medical University (Army Medical Center of PLA), Chongqing, China.
Pathol Res Pract. 2019 Jul;215(7):152448. doi: 10.1016/j.prp.2019.152448. Epub 2019 May 18.
Management of neuroendocrine tumors (NETs) depends on the primary site, but the location of many well-differentiated (WD) NETs is elusive. Organ-specific markers are required for pathological diagnosis from biopsy. Transcription factors with good organ specificity include TTF1 (thyroid transcription factor 1; lung), CDX2 (caudal type homeobox transcription factor 2; midgut), and ISL1 (ISL LIM homeobox 1) and PAX8 (paired box 8) for the pancreas and rectum. SATB2 (SATB homeobox 2) has shown high sensitivity and specificity in colorectal adenocarcinoma. This study determined the viability of SATB2 and other transcription factors as markers, single or in combination, for WD-NETs of various sites.
Immunohistochemical staining of 81 WD-NETs from 8 organ sites was performed to identify SATB2, TTF1, CDX2, ISL1, and PAX8. Receiver operating characteristic (ROC) curves were constructed for different combinations of the 5 markers to determine sensitivity and specificity.
Among the WD-NETs, SATB2 was predominantly found in those of the rectum; TTF1 in the lung, larynx, and esophagus; and ISL1 in the duodenum and rectum. PAX8 and CDX2 showed poor organ specificity. ROC profiles showed 50% sensitivity and 96% specificity to lung for TTF1 ISL1-; and 65% sensitivity and 100% specificity to rectum for SATB2 ISL1- TTF1-. ISL1 SATB2- TTF1- showed 83% sensitivity and 85% specificity to the duodenum, and 44% sensitivity and 87% specificity to the pancreas. A literature search showed that there was no significant difference in the expression rates of the five transcription factors (TTF1, CDX2, SATB2, PAX8 and ISL1) between primary and metastatic WD-NETs at the same organ when there was a large sample size.
Among the 5 transcription factors tested, SATB2 may be a viable marker of WE-NETs of the rectum. The combination of SATB2, ISL1, and TTF1 may help estimate the locations of WD-NETs of unknown origin.
神经内分泌肿瘤（NETs）的治疗取决于肿瘤的原发部位，但许多分化良好（WD）NETs 的位置难以捉摸。从活检中进行病理诊断需要器官特异性标志物。具有良好器官特异性的转录因子包括甲状腺转录因子 1（TTF1；肺）、尾型同源盒转录因子 2（CDX2；中肠）、ISL1（ISL LIM 同源盒 1）和 PAX8（配对盒 8）用于胰腺和直肠。SATB2（SATB 同源盒 2）在结直肠腺癌中具有高灵敏度和特异性。本研究旨在确定 SATB2 和其他转录因子作为标志物的可行性，单独或联合用于各种部位的 WD-NETs。
对 8 个器官部位的 81 例 WD-NETs 进行免疫组织化学染色，以鉴定 SATB2、TTF1、CDX2、ISL1 和 PAX8。为不同的 5 种标志物组合构建接收者操作特征（ROC）曲线，以确定敏感性和特异性。
在 WD-NETs 中，SATB2 主要存在于直肠；TTF1 存在于肺、喉和食管；ISL1 存在于十二指肠和直肠。PAX8 和 CDX2 显示出较差的器官特异性。ROC 图谱显示 TTF1 ISL1-对肺的敏感性为 50%，特异性为 96%；SATB2 ISL1-对直肠的敏感性为 65%，特异性为 100%。ISL1 SATB2- TTF1-对十二指肠的敏感性为 83%，特异性为 85%；对胰腺的敏感性为 44%，特异性为 87%。文献检索显示，当样本量较大时，同一器官的原发性和转移性 WD-NETs 中五种转录因子（TTF1、CDX2、SATB2、PAX8 和 ISL1）的表达率无显著差异。
在测试的 5 种转录因子中，SATB2 可能是直肠 WD-NETs 的可行标志物。SATB2、ISL1 和 TTF1 的组合可能有助于估计来源不明的 WD-NETs 的位置。
