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Loss of expression and prognosis value of alpha-internexin in gastroenteropancreatic neuroendocrine neoplasm.

ABSTRACT: BACKGROUND:The neuronal intermediate filament alpha-internexin (?-internexin) is a cytoskeleton protein which is involved in the tumor initiation and progression. In this study, we examined the expression and prognosis value of ?-internexin in gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). METHODS:?-internexin was detected with immunohistochemical staining in 286 tumor specimens from patients with GEP-NENs. Methylation status of ?-internexin was evaluated by bisulfite genomic sequencing. We assessed the prognostic value of ?-internexin and its correlation with relevant clinicalpathological characteristics. RESULTS:The reduced/loss of expression rate of ?-internexin in GEP-NEN was 73.4% (210/286), while the positive expression rate was 26.6% (76/286). The difference of ?-internexin deficiency was not statistically significant between gastrointestinal NENs (GI-NENs) and pancreatic NENs (pNENs). However, we found significant difference of reduced/loss of ?-internexin expression among different sites of GI-NENs (?2?=?43.470, P?

SUBMITTER: Wang Y

PROVIDER: S-EPMC6020194 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Loss of expression and prognosis value of alpha-internexin in gastroenteropancreatic neuroendocrine neoplasm.

Wang Yuhong Y Chen Yuanjia Y Li Xiaoxing X Hu Wanming W Zhang Yu Y Chen Luohai L Chen Minhu M Chen Jie J

BMC cancer 20180626 1

<h4>Background</h4>The neuronal intermediate filament alpha-internexin (α-internexin) is a cytoskeleton protein which is involved in the tumor initiation and progression. In this study, we examined the expression and prognosis value of α-internexin in gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs).<h4>Methods</h4>α-internexin was detected with immunohistochemical staining in 286 tumor specimens from patients with GEP-NENs. Methylation status of α-internexin was evaluated by bisulfite ...[more]

PMID: 29940892

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Project description:BackgroundNeuroendocrine neoplasm (NEN) is a group of rare tumors. Among which, gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN) is the most common group. The World Health Organization (WHO) classified these tumors into three different grades (G1, G2, and G3) based on Ki-67 and mitotic rate, and updated the classification in 2019. Several previous studies proved that Ki-67 was related to tumor prognosis, but others still reported that Ki-67 had no predictive value for tumor prognosis. There are different conclusions between studies regarding the correlation between Ki-67 and tumor prognosis, and there is a lack of studies about this correlation of GEP-NENs. Further analysis is still needed to evaluate the prognostic value of Ki-67 in GEP-NENs, to provide reference for clinical decisions.MethodsA total of 303 studies were retrieved that included Ki-67, GEP-NENs, prognosis, survival, and other subject terms and keywords. We excluded studies that did not show complete Ki-67 index, number of patients and 5-year survival data available for meta-analysis, non-cohort studies, articles published before 2000 or not published in English. Fifteen studies were finally included to assess the value of Ki-67 in the prognosis of patients with GEP-NENs using a random-effects model.ResultsThe cumulative 5-year survival rate for GEP-NEN G1 (Ki-67 ≤2%), G2 (Ki-67 2-20%) and G3 (Ki-67 >20%) was 86%, 65%, 25% respectively. The 5-year survival rate of GEP-NEN G1 (Ki-67 <3%, first revised in WHO classification 2017, redefined WHO classification 2019) and G1 (Ki-67 ≤2%, WHO classification 2010) was 97% and 84% respectively.ConclusionsThe overall prognosis of GEP-NENs patients showed a decreasing trend with the increase of Ki-67, which confirmed the significance of Ki-67 index as a prognostic marker for the prognosis of GEP-NENs. Increasing the cut-off value of Ki-67 index for G1 grade from ≤2% to <3% according to WHO classification 2019 did not significantly decrease the 5-year survival rate.

Project description:Gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN), considered a heterogeneous neoplasia, exhibit ill-defined pathobiology and protean symptomatology and are ubiquitous in location. They are difficult to diagnose, challenging to manage, and outcome depends on cell type, secretory product, histopathologic grading, and organ of origin. A morphologic and molecular genomic review of these lesions highlights tumor characteristics that can be used clinically, such as somatostatin-receptor expression, and confirms features that set them outside the standard neoplasia paradigm. Their unique pathobiology is useful for developing diagnostics using somatostatin-receptor targeted imaging or uptake of radiolabeled amino acids specific to secretory products or metabolism. Therapy has evolved via targeting of protein kinase B signaling or somatostatin receptors with drugs or isotopes (peptide-receptor radiotherapy). With DNA sequencing, rarely identified activating mutations confirm that tumor suppressor genes are relevant. Genomic approaches focusing on cancer-associated genes and signaling pathways likely will remain uninformative. Their uniquely dissimilar molecular profiles mean individual tumors are unlikely to be easily or uniformly targeted by therapeutics currently linked to standard cancer genetic paradigms. The prevalence of menin mutations in pancreatic NEN and P27KIP1 mutations in small intestinal NEN represents initial steps to identifying a regulatory commonality in GEP-NEN. Transcriptional profiling and network-based analyses may define the cellular toolkit. Multianalyte diagnostic tools facilitate more accurate molecular pathologic delineations of NEN for assessing prognosis and identifying strategies for individualized patient treatment. GEP-NEN remain unique, poorly understood entities, and insight into their pathobiology and molecular mechanisms of growth and metastasis will help identify the diagnostic and therapeutic weaknesses of this neoplasia.

Dataset Information

Loss of expression and prognosis value of alpha-internexin in gastroenteropancreatic neuroendocrine neoplasm.

Publications

Loss of expression and prognosis value of alpha-internexin in gastroenteropancreatic neuroendocrine neoplasm.

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