p27 Loss Is Associated with Poor Prognosis in Gastroenteropancreatic Neuroendocrine Tumors
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PurposeGastroenteropancreatic neuroendocrine tumors (GEP-NETs) represent a heterogeneousdisease group originating from the neuroendocrine cells. Identification of prognosticmarkers, related to neuroendocrine tissue-selective tumorigenesis, is necessary to findtherapeutic targets. Materials and MethodsA 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 150distal colon cases. We performed immunostaining with the tissue microarray method formenin, p27, and p18. ResultsWe observed negative staining for menin, p27, and p18 in 34%, 21%, and 56% ofGEP-NETs, respectively. The loss of p27, but not menin, was positively correlated with thegrade of Ki-67. Menin–/p27–, menin–/p27+, menin+/p27–, and menin+/p27+ phenotypegroups included 13%, 22%, 8%, and 57% of patients, respectively. A dichotomizedcomparison showed that menin– or p27– tumors were significantly associated with foregutand midgut localizations, high World Health Organization (WHO) grade, lymph nodemetastasis, and more advanced stage as compared to menin+/p27+ patients. Kaplan-Meier analysis for the overall survival showed that p27 loss was significantlyassociated with decreased survival. Multivariate analysis showed that p27 loss is anindependent factor for poor overall survival. ConclusionOur results revealed that the loss of p27 is associated with poor prognosis and themenin-p27 pathway is important in the tumorigenesis of GEP-NETs.
Abstract
PurposeGastroenteropancreatic neuroendocrine tumors (GEP-NETs) represent a heterogeneousdisease group originating from the neuroendocrine cells. Identification of prognosticmarkers, related to neuroendocrine tissue-selective tumorigenesis, is necessary to findtherapeutic targets. Materials and MethodsA 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 150distal colon cases. We performed immunostaining with the tissue microarray method formenin, p27, and p18. ResultsWe observed negative staining for menin, p27, and p18 in 34%, 21%, and 56% ofGEP-NETs, respectively. The loss of p27, but not menin, was positively correlated with thegrade of Ki-67. Menin–/p27–, menin–/p27+, menin+/p27–, and menin+/p27+ phenotypegroups included 13%, 22%, 8%, and 57% of patients, respectively. A dichotomizedcomparison showed that menin– or p27– tumors were significantly associated with foregutand midgut localizations, high World Health Organization (WHO) grade, lymph nodemetastasis, and more advanced stage as compared to menin+/p27+ patients. Kaplan-Meier analysis for the overall survival showed that p27 loss was significantlyassociated with decreased survival. Multivariate analysis showed that p27 loss is anindependent factor for poor overall survival. ConclusionOur results revealed that the loss of p27 is associated with poor prognosis and themenin-p27 pathway is important in the tumorigenesis of GEP-NETs.
참고문헌 (22)
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