Abstract:
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.
摘要:
Hand2是负责嗜铬细胞分化的核心转录因子。然而,尚未研究其在手术病理学中的潜在用途。因此,我们旨在研究其在副神经节瘤中的表达,其他神经内分泌肿瘤,和其他非神经内分泌肿瘤。我们在肾上腺髓质细胞上校准了Hand2免疫组织化学,并分析了46个副神经节瘤(PG)的H评分,9个转移性PG,21名马尾神经内分泌肿瘤(CENET),48个神经内分泌癌(NEC),8个嗅觉神经母细胞瘤(ONBs),110个分化良好的NETs(WDNETs),10肾上腺皮质癌,29肾上腺皮质腺瘤,8个黑色素瘤,41种不同的癌症,和10个胃肠道间质瘤(GIST)。研究了组织微阵列(TMA)和整个切片(WS)。在171个NENs中,先前发表的关于Phox2B和GATA3的数据与Hand2相关。Hand2在98.1%(54/55)PG中呈阳性,但在WDNETs中很少见(9.6%,10/104),CENET(9.5%,2/21),NEC(4.2%,2/48),或ONB(12.5%,1/8)。对于PG的诊断,任何Hand2阳性的敏感性为98.1%,特异性为91.7%。与Hand2阳性WDNETs相比,主要PG中的Hand2H评分明显更高(中位数为166.3vs.7.5;p<0.0001)。转移性PG阳性占88.9%(8/9)。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,8/10GIST除外。与交感PG相比,副交感PG显示出较高的Hand2H评分(中位数H评分280与104,p<0.0001)。NENs中的Hand2阳性是原发性和转移性PG的可靠标志物,因为其他NENs很少表现出有限的Hand2阳性。