Ladenheim Alexander, Zheng Jasper X, Teklu Abebe, Matsukuma Karen
Department of Pathology and Laboratory Medicine, University of California, Davis School of Medicine, Sacramento, CA, USA.
Int J Surg Pathol. 2025 Feb;33(1):76-84. doi: 10.1177/10668969241260208. Epub 2024 Jul 21.
A number of immunohistochemical stains have been examined for utility in establishing the site of origin for metastatic well-differentiated neuroendocrine tumors (NETs). In the gastrointestinal (GI) tract, distinguishing metastatic duodenal NETs from jejunoileal and other GI NETs is important for clinical work-up, prognosis, and therapy. A recent study indicated that prohormone convertase 2 (PCSK2 or PC2) had broad expression in small intestine and appendiceal NETs. Because the study did not include duodenal NETs, we examined PCSK2 expression in duodenal and other GI NETs.
GI NETs (n = 69) and 13 corresponding lymph node metastases from stomach, duodenum, pancreas, ileum, appendix, and rectum were evaluated for the expression of PCSK2, along with ISL1, NKX2.2, CDX2, SATB2, and PAX8. Expression of each stain was evaluated using the H-score system, and differences in expression by site were evaluated by the chi square test.
PCSK2 was expressed at similar frequency in duodenal (50%), pancreatic (59%), and ileal NETs (40%). PCSK2 was infrequently expressed in stomach (0%), appendiceal (8%), and rectal (25%) NETs. However, incorporating PCSK2 into a panel including ISL1, NKX2.2, CDX2, and SATB2 allowed development of an algorithm which had 87% sensitivity and 93% specificity for classification of ileal NETs; and 68% sensitivity and 98% specificity for pancreaticoduodenal NETs.
In contrast to previous findings, PCSK2 does not show specificity for any particular GI site. An algorithmic approach incorporating the expression of PCSK2 with that of ISL1, NKX2.2, CDX2, and SATB2 is useful in discriminating pancreatic, duodenal, ileal, appendiceal, and rectal NETs.
已经对多种免疫组织化学染色方法在确定转移性高分化神经内分泌肿瘤（NETs）的原发部位方面的实用性进行了研究。在胃肠道（GI）中，区分转移性十二指肠NETs与空肠回肠及其他胃肠道NETs对于临床检查、预后评估和治疗至关重要。最近一项研究表明，激素原转化酶2（PCSK2或PC2）在小肠和阑尾NETs中广泛表达。由于该研究未纳入十二指肠NETs，我们检测了PCSK2在十二指肠及其他胃肠道NETs中的表达情况。
对69例胃肠道NETs以及来自胃、十二指肠、胰腺、回肠、阑尾和直肠的13个相应淋巴结转移灶进行检测，评估PCSK2以及ISL1、NKX2.2、CDX2、SATB2和PAX8的表达情况。使用H评分系统评估每种染色的表达情况，并通过卡方检验评估不同部位表达的差异。
PCSK2在十二指肠NETs（50%）、胰腺NETs（59%）和回肠NETs（40%）中的表达频率相似。PCSK2在胃NETs（0%）、阑尾NETs（8%）和直肠NETs（25%）中很少表达。然而，将PCSK2纳入包括ISL1、NKX2.2、CDX2和SATB2的检测组合中，可以开发出一种算法，该算法对回肠NETs分类的敏感性为87%，特异性为93%；对胰十二指肠NETs的敏感性为68%，特异性为98%。
与之前的研究结果相反，PCSK2对任何特定的胃肠道部位均无特异性。将PCSK2的表达与ISL1、NKX2.2、CDX2和SATB2的表达相结合的算法方法，有助于鉴别胰腺、十二指肠、回肠、阑尾和直肠NETs。
