Soukup Jiri, Manethova Monika, Stejskal Vaclav, Novakova Marie, Duskova Jaroslava, Hornychova Helena, Hacova Maria, Staniczkova-Zambo Iva, Zelinka Tomas, Kosak Mikulas, Cesak Tomas, Netuka David, Ryska Ales, Gabalec Filip
Department of Pathology, Military University Hospital Prague, U Vojenske Nemocnice 1200, Praha 6, 169 02, Prague, Czech Republic.
The Fingerland Department of Pathology, Charles University, Faculty of Medicine in Hradec Králové and University Hospital Hradec Králové, Sokolska 582, 500 05, Hradec Kralove, Czech Republic.
Endocr Pathol. 2024 Mar;35(1):14-24. doi: 10.1007/s12022-024-09803-6. Epub 2024 Feb 28.
Hand2 is a core transcription factor responsible for chromaffin cell differentiation. However, its potential utility in surgical pathology has not been studied. Thus, we aimed to investigate its expression in paragangliomas, other neuroendocrine neoplasms (NENs), and additional non-neuroendocrine tumors. We calibrated Hand2 immunohistochemistry on adrenal medulla cells and analyzed H-scores in 46 paragangliomas (PGs), 9 metastatic PGs, 21 cauda equina neuroendocrine tumors (CENETs), 48 neuroendocrine carcinomas (NECs), 8 olfactory neuroblastomas (ONBs), 110 well-differentiated NETs (WDNETs), 10 adrenal cortical carcinomas, 29 adrenal cortical adenomas, 8 melanomas, 41 different carcinomas, and 10 gastrointestinal stromal tumors (GISTs). Both tissue microarrays (TMAs) and whole sections (WSs) were studied. In 171 NENs, previously published data on Phox2B and GATA3 were correlated with Hand2. Hand2 was positive in 98.1% (54/55) PGs, but only rarely in WDNETs (9.6%, 10/104), CENETs (9.5%, 2/21), NECs (4.2%, 2/48), or ONBs (12.5%, 1/8). Any Hand2 positivity was 98.1% sensitive and 91.7% specific for the diagnosis of PG. The Hand2 H-score was significantly higher in primary PGs compared to Hand2-positive WDNETs (median 166.3 vs. 7.5; p < 0.0001). Metastatic PGs were positive in 88.9% (8/9). No Hand2 positivity was observed in any adrenal cortical neoplasm or other non-neuroendocrine tumors, with exception of 8/10 GISTs. Parasympathetic PGs showed a higher Hand2 H-score compared to sympathetic PGs (median H-scores 280 vs. 104, p < 0.0001). Hand2 positivity in NENs serves as a reliable marker of primary and metastatic PG, since other NENs only rarely exhibit limited Hand2 positivity.
Hand2是一种负责嗜铬细胞分化的核心转录因子。然而，其在外科病理学中的潜在用途尚未得到研究。因此，我们旨在研究其在副神经节瘤、其他神经内分泌肿瘤（NENs）以及其他非神经内分泌肿瘤中的表达情况。我们对肾上腺髓质细胞进行了Hand2免疫组织化学校准，并分析了46例副神经节瘤（PGs）、9例转移性PGs、21例马尾神经内分泌肿瘤（CENETs）、48例神经内分泌癌（NECs）、8例嗅神经母细胞瘤（ONBs）、110例高分化神经内分泌肿瘤（WDNETs）、10例肾上腺皮质癌、29例肾上腺皮质腺瘤、8例黑色素瘤以及41例不同类型的癌和10例胃肠道间质瘤（GISTs）的H评分。同时研究了组织微阵列（TMAs）和全切片（WSs）。在171例NENs中，将先前发表的关于Phox2B和GATA3的数据与Hand2进行了相关性分析。Hand2在98.1%（54/55）的PGs中呈阳性，但在WDNETs（9.6%，10/104）、CENETs（9.5%，2/21）、NECs（4.2%，2/48）或ONBs（12.5%，1/8）中仅很少呈阳性。Hand2的任何阳性对PG诊断的敏感性为98.1%，特异性为91.7%。与Hand2阳性的WDNETs相比，原发性PGs的Hand2 H评分显著更高（中位数分别为166.3和7.5；p < 0.0001）。转移性PGs的阳性率为88.9%（8/9）。除8/10的GISTs外，在任何肾上腺皮质肿瘤或其他非神经内分泌肿瘤中均未观察到Hand2阳性。与交感神经PGs相比，副交感神经PGs的Hand2 H评分更高（中位数H评分分别为280和104，p < 0.0001）。由于其他NENs仅很少表现出有限的Hand2阳性，因此NENs中的Hand2阳性是原发性和转移性PG的可靠标志物。
