Institute of Pharmacology and Toxicology, Jena University Hospital, Friedrich Schiller University Jena, Drackendorfer Str. 1, 07747, Jena, Germany.
Department of General and Visceral Surgery, Zentralklinik Bad Berka, Bad Berka, Germany.
Sci Rep. 2022 Aug 30;12(1):14722. doi: 10.1038/s41598-022-19014-w.
Somatostatin receptors SST1, SST2, and SST5 are overexpressed in neuroendocrine neoplasms (NENs), but little is known about SST4 expression in NENs because of a lack of specific monoclonal antibodies. We recently developed and thoroughly characterised a rabbit monoclonal anti-human SST4 antibody, 7H49L61, and showed that it is well suited for identifying SST4 expression in routine pathology samples. The present study aimed to re-evaluate SST4 expression in a large set of NEN samples using this antibody. For this purpose, we assessed SST4 expression in 722 formalin-fixed, paraffin-embedded NEN samples from 274 patients by immunohistochemistry using the novel antibody 7H49L61. The immunostaining was semiquantitatively evaluated using the 12-point immunoreactivity score (IRS), and the results were correlated with clinicopathological data. SST4 was detected in 39.3% of all NENs, but with a median IRS of 2.0, its expression intensity was negligible overall. In all cases, both cytoplasmic and membraneous staining was observed. SST4 expression was somewhat higher in bronchopulmonary NEN (BP-NEN) than in gastroenteropancreatic NEN (GEP-NEN) but still very low. SST4 expression positively correlated with favourable patient outcomes in BP-NEN but had a positive association with Ki-67 index or tumour grading and a negative interrelationship with overall survival in GEP-NEN. In conclusion, unlike that of other SST subtypes, SST4 expression in both BP-NEN and GEP-NEN is negligible and of no diagnostic or therapeutic relevance.
生长抑素受体 SST1、SST2 和 SST5 在神经内分泌肿瘤（NEN）中过表达，但由于缺乏特异性单克隆抗体，对 SST4 在 NEN 中的表达知之甚少。我们最近开发并彻底表征了一种兔单克隆抗人 SST4 抗体 7H49L61，并表明它非常适合识别常规病理样本中的 SST4 表达。本研究旨在使用该抗体重新评估大量 NEN 样本中的 SST4 表达。为此，我们使用新型抗体 7H49L61 通过免疫组织化学评估了 274 名患者的 722 例福尔马林固定、石蜡包埋的 NEN 样本中的 SST4 表达。使用 12 分免疫反应性评分（IRS）对免疫染色进行半定量评估，并将结果与临床病理数据相关联。SST4 在所有 NEN 中的检出率为 39.3%，但 IRS 中位数为 2.0，总体表达强度可忽略不计。在所有情况下，均观察到细胞质和膜染色。与胃肠胰神经内分泌肿瘤（GEP-NEN）相比，支气管肺神经内分泌肿瘤（BP-NEN）中的 SST4 表达略高，但仍然非常低。SST4 表达与 BP-NEN 患者的良好预后呈正相关，但与 Ki-67 指数或肿瘤分级呈正相关，与 GEP-NEN 的总生存期呈负相关。总之，与其他 SST 亚型不同，BP-NEN 和 GEP-NEN 中的 SST4 表达可忽略不计，且无诊断或治疗意义。
