Abstract：
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.
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.
摘要：
已经检查了许多免疫组织化学染色在建立转移性高分化神经内分泌肿瘤（NET）的起源部位中的实用性。在胃肠道（GI），区分转移性十二指肠NETs与空肠和其他GINETs对于临床检查很重要，预后,和治疗。最近的一项研究表明，激素原转化酶2（PCSK2或PC2）在小肠和阑尾NETs中广泛表达。因为这项研究不包括十二指肠NET，我们检测了PCSK2在十二指肠和其他GINETs中的表达。
GINETs（n=69）和13个相应的胃淋巴结转移，十二指肠,胰腺,回肠,附录,和直肠评估PCSK2的表达，以及ISL1，NKX2.2，CDX2，SATB2和PAX8。使用H评分系统评估每种染色的表达，通过卡方检验评估不同部位的表达差异。
PCSK2在十二指肠中的表达频率相似（50％），胰腺（59％），和回肠NETs(40%)。PCSK2在胃中很少表达（0%），阑尾（8%），和直肠（25％）NET。然而,将PCSK2纳入包括ISL1,NKX2.2,CDX2和SATB2的组,可以开发一种算法,该算法对回肠NETs的分类具有87%的灵敏度和93%的特异性;对胰十二指肠NETs的灵敏度和特异性分别为68%和98%.
与之前的发现相比，PCSK2不显示对任何特定GI位点的特异性。将PCSK2的表达与ISL1，NKX2.2，CDX2和SATB2的表达相结合的算法方法可用于区分胰腺，十二指肠,回肠,阑尾,直肠NET。
GINETs（n=69）和13个相应的胃淋巴结转移，十二指肠,胰腺,回肠,附录,和直肠评估PCSK2的表达，以及ISL1，NKX2.2，CDX2，SATB2和PAX8。使用H评分系统评估每种染色的表达，通过卡方检验评估不同部位的表达差异。
PCSK2在十二指肠中的表达频率相似（50％），胰腺（59％），和回肠NETs(40%)。PCSK2在胃中很少表达（0%），阑尾（8%），和直肠（25％）NET。然而,将PCSK2纳入包括ISL1,NKX2.2,CDX2和SATB2的组,可以开发一种算法,该算法对回肠NETs的分类具有87%的灵敏度和93%的特异性;对胰十二指肠NETs的灵敏度和特异性分别为68%和98%.
与之前的发现相比，PCSK2不显示对任何特定GI位点的特异性。将PCSK2的表达与ISL1，NKX2.2，CDX2和SATB2的表达相结合的算法方法可用于区分胰腺，十二指肠,回肠,阑尾,直肠NET。
