The Fingerland Department of Pathology, Charles University, Faculty of Medicine in Hradec Králové and University Hospital Hradec Králové, Hradec Králové, Czech Republic.
Department of Medical Biology and Genetics, Charles University, Faculty of Medicine in Hradec Králové, Hradec Králové, Czech Republic.
Histopathology. 2022 Dec;81(6):799-807. doi: 10.1111/his.14789. Epub 2022 Sep 22.
Pitx2 is a transcription factor responsible for establishment of the right-left axis and development of the gut and pituitary. In mouse embryos, Pitx2 is expressed in the greater curvature of the stomach and midgut. Previously, Pitx2 was studied in pituitary neuroendocrine tumours but not in other NETs. Pitx2 expression was immunohistochemically assessed in whole sections and tissue microarrays in a cohort of 224 neuroendocrine neoplasms, and was analysed in 29 cases. The cohort included 18 cauda equina NETs, 38 paragangliomas, 98 cases of primary visceral NETs from different organs, 23 metastases of visceral NETs and 47 neuroendocrine carcinomas (NECs). Pitx2 expression was observed in 29.5% (29 of 98) NETs and 14.9% (7 of 47) NECs, but was not observed in any paraganglioma or cauda equina NET. Pitx2 was observed only in tumours of midgut-derived organs, including the small intestine (100%, 20 of 20), appendix (88.9%, eight of nine) and large intestine (9.1%, one of 11 - only caecal NET). The NETs of remaining locations were negative. Pitx2 was 96.7% sensitive and 100% specific for NETs of midgut origin. In NECs, Pitx2 positivity was observed in goblet cell adenocarcinoma (75%, three of four), medullary thyroid carcinoma (42.9, three of seven) and one Merkel cell carcinoma (25%, one of four). In metastatic NETs, Pitx2 was observed in all the tumours originating in the small intestine (n = 17) or caecum (n = 1). No positivity was observed in tumours from other locations (four pancreas, one lung). We observed no correlation between immunoreactivity and mRNA expression. Thus, Pitx2 immunohistochemistry can be helpful in assessing the midgut origin of NETs.
Pitx2 是一种转录因子，负责建立左右轴和胃肠道以及垂体的发育。在小鼠胚胎中，Pitx2 表达于胃的大弯和中肠。先前，Pitx2 在垂体神经内分泌肿瘤中进行了研究，但不在其他 NETs 中进行研究。在一个包含 224 例神经内分泌肿瘤的队列中，通过全切片和组织微阵列对 Pitx2 表达进行了免疫组织化学评估，并对 29 例病例进行了分析。该队列包括 18 例马尾神经 NETs、38 例副神经节瘤、98 例来自不同器官的原发性内脏 NETs、23 例内脏 NET 转移瘤和 47 例神经内分泌癌（NECs）。Pitx2 表达见于 29.5%（98 例 NETs 中的 29 例）和 14.9%（47 例 NECs 中的 7 例），但未见于任何副神经节瘤或马尾神经 NETs。Pitx2 仅见于来源于中肠器官的肿瘤，包括小肠（100%，20/20）、阑尾（88.9%，9/9）和大肠（9.1%，11 例中仅 1 例——仅升结肠 NET）。其余部位的 NETs 均为阴性。Pitx2 对来源于中肠的 NETs 的敏感性为 96.7%，特异性为 100%。在 NECs 中，Pitx2 阳性见于杯状细胞腺癌（75%，4/4）、甲状腺髓样癌（42.9%，7/7）和 1 例 Merkel 细胞癌（25%，4/4）。在转移性 NETs 中，Pitx2 见于源自小肠（n=17）或盲肠（n=1）的所有肿瘤。在源自其他部位的肿瘤中未见阳性（4 例胰腺，1 例肺）。我们观察到免疫反应性与 mRNA 表达之间无相关性。因此，Pitx2 免疫组化有助于评估 NETs 的中肠起源。
