Expression of gremlin 1 correlates with increased angiogenesis and progression-free survival in patients with pancreatic neuroendocrine tumors.
BACKGROUND
Gremlin 1 (GREM1) is a bone morphogenetic protein antagonist and a novel proangiogenic factor. Our aim was to evaluate the prognostic value of GREM1 expression and GREM1-related factors in tumor-associated angiogenesis in pancreatic neuroendocrine tumors (NETs).


METHODS
The immunohistochemical expression of GREM1 and microvessel density (MVD) were examined in 35 patients with pancreatic NETs and then compared with other clinicopathologic characteristics, including the World Health Organization classification.


RESULTS
The presence of expression of GREM1 (p = 0.016) and high MVD (p = 0.020) were significant and favorable prognostic factors. Moreover, GREM1 expression was significantly associated with high MVD (p = 0.011). MVD was significantly higher in well-differentiated NETs than in well-differentiated or poorly differentiated neuroendocrine carcinomas (p < 0.001).


CONCLUSIONS
GREM1 expression was correlated with tumor-associated angiogenesis and was found to be a novel prognostic marker in pancreatic NETS. Our data support a tumor suppressor role of GREM1 in pancreatic NETs.
Institute of Clinical Medicine, National Yang-Ming University, No. 155, Sec. 2, Linong St., Taipei, 112, Taiwan.
Ming-Huang
MH
Chen
Yi-Chen
YC
Yeh
Yi-Ming
YM
Shyr
Yi-Hua
YH
Jan
Yee
Y
Chao
Chung-Pin
CP
Li
Shin-E
SE
Wang
Cheng-Hwai
CH
Tzeng
Peter Mu-Hsin
PM
Chang
Chun-Yu
CY
Liu
Ming-Han
MH
Chen
Michael
M
Hsiao
Chi-Ying F
CY
Huang
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008297:Male; D055806:Microvessels / Q000473:pathology; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D018358:Neuroendocrine Tumors / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D010190:Pancreatic Neoplasms / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D055815:Young Adult
D014408:Biomarkers, Tumor; C486399:GREM1 protein, human; D036341:Intercellular Signaling Peptides and Proteins