p27 Loss Is Associated with Poor Prognosis in Gastroenteropancreatic Neuroendocrine Tumors.
- Author:
Hee Sung KIM
1
;
Hye Seung LEE
;
Kyung Han NAM
;
Jiwoon CHOI
;
Woo Ho KIM
Author Information
- Publication Type:Original Article
- Keywords: Cyclin-dependent kinase inhibitor p27; Menin; Neuroendocrine tumors; Gastrointestinal neoplasms; Pancreatic neoplasms; Prognosis; Biological tumor markers
- MeSH: Carcinogenesis; Colon; Cyclin-Dependent Kinase Inhibitor p27; Gastrointestinal Neoplasms; Humans; Kaplan-Meier Estimate; Lymph Nodes; Multivariate Analysis; Negative Staining; Neoplasm Metastasis; Neuroendocrine Cells; Neuroendocrine Tumors*; Pancreatic Neoplasms; Phenotype; Prognosis*; Biomarkers, Tumor; World Health Organization
- From:Cancer Research and Treatment 2014;46(4):383-392
- CountryRepublic of Korea
- Language:English
- Abstract: PURPOSE: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) represent a heterogeneous disease group originating from the neuroendocrine cells. Identification of prognostic markers, related to neuroendocrine tissue-selective tumorigenesis, is necessary to find therapeutic targets. MATERIALS AND METHODS: A total of 327 patients with GEP-NETs were included in this study; there were 49 gastric, 29 duodenal, 49 pancreatic, 12 hepatobiliary, 33 appendiceal, 5 proximal colon, and 150 distal colon cases. We performed immunostaining with the tissue microarray method for menin, p27, and p18. RESULTS: We observed negative staining for menin, p27, and p18 in 34%, 21%, and 56% of GEP-NETs, respectively. The loss of p27, but not menin, was positively correlated with the grade of Ki-67. Menin-/p27-, menin-/p27+, menin+/p27-, and menin+/p27+ phenotype groups included 13%, 22%, 8%, and 57% of patients, respectively. A dichotomized comparison showed that menin- or p27- tumors were significantly associated with foregut and midgut localizations, high World Health Organization (WHO) grade, lymph node metastasis, and more advanced stage as compared to menin+/p27+ patients. Kaplan-Meier analysis for the overall survival showed that p27 loss was significantly associated with decreased survival. Multivariate analysis showed that p27 loss is an independent factor for poor overall survival. CONCLUSION: Our results revealed that the loss of p27 is associated with poor prognosis and the menin-p27 pathway is important in the tumorigenesis of GEP-NETs.
