Expression of Sex Determining Region Y-Box 2 and Pancreatic and Duodenal Homeobox 1 in Pancreatic Neuroendocrine Tumors.
OBJECTIVE
The World Health Organization 2010 classification divides pancreatic neuroendocrine tumors (p-NETs) entity to well-differentiated neuroendocrine tumors (NET) and poorly differentiated neuroendocrine carcinomas (NEC) by Ki-67 index. The aim of this study is elucidate the pathophysiology and tumor biology of p-NETs.


METHODS
We assessed the expression of transcription factors sex determining region Y-box 2 (SOX2) and pancreatic and duodenal homeobox 1 (Pdx1)) essential for the normal fetal development of pancreatic neuroendocrine cells in 46 surgically resected p-NETs by immunohistochemistry. The relationship of expression levels of these factors and clinicopathological factors were analyzed.


RESULTS
SOX2 was positive in 6 p-NETs (13.0%). Five of 7 NEC patients showed positive for SOX2. SOX2 was highly (sensitivity 71%) and specifically (specificity 97%) expressed in NEC. Patients with SOX2 positive p-NET showed the significantly shorter disease-free and overall survival than patients with SOX2 negative p-NET. High Pdx1 expression was seen in 25 p-NET patients (54.3%). None of the NEC patients showed high Pdx1 expression. There was a significant reverse correlation between SOX2 and Pdx1 expression.


CONCLUSIONS
The expression patterns of SOX2 and Pdx1 highly correlated with prognosis of p-NETs. These expression patterns may represent the biological and pathophysiological difference of p-NETs and indicate the origin of tumor.
From the Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba City, Chiba, Japan.
Takahiro
T
Akiyama
Takashi
T
Shida
Hideyuki
H
Yoshitomi
Shigetsugu
S
Takano
Shingo
S
Kagawa
Hiroaki
H
Shimizu
Masayuki
M
Ohtsuka
Atsushi
A
Kato
Katsunori
K
Furukawa
Masaru
M
Miyazaki
D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D016009:Chi-Square Distribution; D005260:Female; D018398:Homeodomain Proteins / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000378:metabolism* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D055748:SOXB1 Transcription Factors / Q000096:biosynthesis*; D015534:Trans-Activators / Q000096:biosynthesis*
D014408:Biomarkers, Tumor; D018398:Homeodomain Proteins; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein