Expression of cadherin 17 in well-differentiated neuroendocrine tumours.
OBJECTIVE
Cadherin 17 (CDH17) is expressed primarily in normal intestinal epithelium and digestive tract tumours, and has limited expression in other neoplasms. The aims of this study were to examine CDH17 expression in well-differentiated neuroendocrine tumours (WDNETs) from various primary sites, representing the foregut, midgut, and hindgut, and tumours metastasizing to the liver, and to correlate the differences between the expression of CDH17, CDX2, and thyroid transcription factor 1 (TTF1).


RESULTS
We investigated CDH17 immunohistochemical expression in 150 primary WDNETs from eight anatomical sites, including 68 from the foregut, 70 from the midgut, and 12 from the hindgut, and 15 metastases. CDH17 immunoreactivity increased significantly from foregut to hindgut WDNETs (P < 0.0001). Pancreatic WDNETs expressed CDH17 at a significantly higher frequency than other foregut tumours. Within the midgut, appendiceal and small-intestinal WDNETs were more frequently positive for CDH17 than for CDX2. All hindgut WDNETs expressed CDH17, in contrast to CDX2 (positive in one rectal case). CDH17 expression in liver metastases was similar to that of the primary tumours.


CONCLUSIONS
This study is the first to comprehensively examine CDH17 expression in WDNETs from different sites. CDH17 is a sensitive marker for midgut WDNETs, and the CDH17+/CDX2-/TTF1- phenotype was found to be sensitive (92%) and specific (91%) for hindgut WDNETs.
Department of Pathology, Rhode Island Hospital and Alpert Medical School of Brown University, Providence, RI, USA.|Department of Pathology, University of Iowa Hospitals and Clinics, Iowa City, IA, USA.
Anthony N
AN
Snow
Department of Pathology, Rhode Island Hospital and Alpert Medical School of Brown University, Providence, RI, USA.
Shamlal
S
Mangray
Department of Pathology, Rhode Island Hospital and Alpert Medical School of Brown University, Providence, RI, USA.
Shaolei
S
Lu
Department of Pathology, Rhode Island Hospital and Alpert Medical School of Brown University, Providence, RI, USA.
Rashna
R
Clubwala
Department of Pathology, Rhode Island Hospital and Alpert Medical School of Brown University, Providence, RI, USA.
Jianhong
J
Li
Department of Pathology, Rhode Island Hospital and Alpert Medical School of Brown University, Providence, RI, USA.
Murray B
MB
Resnick
Department of Pathology, Rhode Island Hospital and Alpert Medical School of Brown University, Providence, RI, USA.
Evgeny
E
Yakirevich
D014408:Biomarkers, Tumor / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007414:Intestinal Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D018358:Neuroendocrine Tumors / Q000378:metabolism* / Q000473:pathology; D014157:Transcription Factors
D014408:Biomarkers, Tumor; C490584:CDH17 protein, human; D015820:Cadherins; D004268:DNA-Binding Proteins; C504003:TTF1 protein, human; D014157:Transcription Factors
CDH17; CDX2; TTF1; cadherin17; neuroendocrine tumour