Phosphohistone H3 and Ki-67 Labeling Indices in Cytologic Specimens from Well-Differentiated Neuroendocrine Tumors of the Gastrointestinal Tract and Pancreas: A Comparative Analysis Using Automated Image Cytometry

2013 ◽  
Vol 57 (5) ◽  
pp. 501-508 ◽  
Author(s):  
Adele D. Fung ◽  
Cynthia Cohen ◽  
Sravankumar Kavuri ◽  
Diane Lawson ◽  
Xin Gao ◽  
...  
Keyword(s):  
Comparative Analysis ◽  
Gastrointestinal Tract ◽  
Neuroendocrine Tumors ◽  
Image Cytometry ◽  
Ki 67 ◽  
Phosphohistone H3 ◽  
Well Differentiated

scholarly journals Identification of Phosphohistone H3 Cutoff Values Corresponding to Original WHO Grades but Distinguishable in Well-Differentiated Gastrointestinal Neuroendocrine Tumors

2018 ◽  
Vol 2018 ◽  
pp. 1-10
Author(s):  
Min Jeong Kim ◽  
Mi Jung Kwon ◽  
Ho Suk Kang ◽  
Kyung Chan Choi ◽  
Eun Sook Nam ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Disease Free Survival ◽  
World Health ◽  
Grading System ◽  
Specific Marker ◽  
Ki 67 ◽  
Cutoff Values ◽  
Phosphohistone H3 ◽  
Well Differentiated ◽  
Health Organization

Mitotic counts in the World Health Organization (WHO) grading system have narrow cutoff values. True mitotic figures, however, are not always distinguishable from apoptotic bodies and darkly stained nuclei, complicating the ability of the WHO grading system to diagnose well-differentiated neuroendocrine tumors (NETs). The mitosis-specific marker phosphohistone H3 (PHH3) can identify true mitoses and grade tumors reliably. The aim of this study was to investigate the correspondence of tumor grades, as determined by PHH3 mitotic index (MI) and mitotic counts according to WHO criteria, and to determine the clinically relevant cutoffs of PHH3 MI in rectal and nonrectal gastrointestinal NETs. Mitotic counts correlated with both the Ki-67 labeling index and PHH3 MI, but the correlation with PHH3 MI was slightly higher. The PHH3 MI cutoff ≥4 correlated most closely with original WHO grades for both rectal NETs. A PHH3 MI cutoff ≥4, which could distinguish between G1 and G2 tumors, was associated with disease-free survival in patients with rectal NETs, whereas that cutoff value showed marginal significance for overall survival in patient with rectal NETs. In conclusion, the use of PHH3 ≥4 correlated most closely with original WHO grades.

scholarly journals Molecular Pathology of Well-Differentiated Pulmonary and Thymic Neuroendocrine Tumors: What Do Pathologists Need to Know?

2021 ◽  
Vol 32 (1) ◽  
pp. 154-168 ◽  
Author(s):  
Marco Volante ◽  
Ozgur Mete ◽  
Giuseppe Pelosi ◽  
Anja C. Roden ◽  
Ernst Jan M. Speel ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Young Patients ◽  
Carcinoid Tumors ◽  
Neuroendocrine Neoplasms ◽  
Grey Zone ◽  
Cell Hyperplasia ◽  
Ki 67 ◽  
Familial Form ◽  
Well Differentiated ◽  
Neuroendocrine Carcinomas

AbstractThoracic (pulmonary and thymic) neuroendocrine tumors are well-differentiated epithelial neuroendocrine neoplasms that are classified into typical and atypical carcinoid tumors based on mitotic index cut offs and presence or absence of necrosis. This classification scheme is of great prognostic value but designed for surgical specimens, only. Deep molecular characterization of thoracic neuroendocrine tumors highlighted their difference with neuroendocrine carcinomas. Neuroendocrine tumors of the lung are characterized by a low mutational burden, and a high prevalence of mutations in chromatin remodeling and histone modification-related genes, whereas mutations in genes frequently altered in neuroendocrine carcinomas are rare. Molecular profiling divided thymic neuroendocrine tumors into three clusters with distinct clinical outcomes and characterized by a different average of copy number instability. Moreover, integrated histopathological, molecular and clinical evidence supports the existence of a grey zone category between neuroendocrine tumors (carcinoid tumors) and neuroendocrine carcinomas. Indeed, cases with well differentiated morphology but mitotic/Ki-67 indexes close to neuroendocrine carcinomas have been increasingly recognized. These are characterized by specific molecular profiles and have an aggressive clinical behavior. Finally, thoracic neuroendocrine tumors may arise in the background of genetic susceptibility, being MEN1 syndrome the well-defined familial form. However, pathologists should be aware of rarer germline variants that are associated with the concurrence of neuroendocrine tumors of the lung or their precursors (such as DIPNECH) with other neoplasms, including but not limited to breast carcinomas. Therefore, genetic counseling for all young patients with thoracic neuroendocrine neoplasia and/or any patient with pathological evidence of neuroendocrine cell hyperplasia-to-neoplasia progression sequence or multifocal disease should be considered.

Erratum to: KI-67 heterogeneity in well differentiated gastro-entero-pancreatic neuroendocrine tumors: when is biopsy reliable for grade assessment?

Endocrine ◽  
2017 ◽  
Vol 57 (3) ◽  
pp. 503-503
Author(s):  
Federica Grillo ◽  
Luca Valle ◽  
Diego Ferone ◽  
Manuela Albertelli ◽  
Maria Pia Brisigotti ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Pancreatic Neuroendocrine Tumors ◽  
Ki 67 ◽  
Well Differentiated ◽  
Grade Assessment

scholarly journals Expression of the phosphorylated variant of the AKT1-kinase (p-AKT1) in well-differentiated pancreatic neuroendocrine tumors: immunohistochemical evaluation

2018 ◽  
Vol 46 (4) ◽  
pp. 314-322
Author(s):  
V. V. Delektorskaya ◽  
O. N. Solov'eva ◽  
G. Yu. Chemeris ◽  
Yu. I. Patyutko
Keyword(s):  
Liver Metastases ◽  
Neuroendocrine Tumors ◽  
Treatment Effectiveness ◽  
Disease Free Survival ◽  
Immunohistochemical Analysis ◽  
Pancreatic Neuroendocrine Tumors ◽  
Ki 67 ◽  
New Treatment ◽  
Well Differentiated ◽  
High Level

Background:Well-differentiated pancreatic neuroendocrine tumors (pNETs) represent a group of rare epithelial neoplasms with a highly variable clinical course. AKT1 is one of the most frequently activated protein kinases in pNETs, which promotes the tumor growth and is of interest as a prognostic factor and a target for new treatment approaches.Aim:To study the expression of the phosphorylated variant of AKT1-kinase (p-AKT1) in primary pNETs and their liver metastases and to correlate the results with various clinical and pathological parameters and the disease prognosis.Materials and methods:P-AKT1 expression was studied by the immunohistochemical analysis of the primary lesions and liver metastases in 52 pNETs patients.Results:A high level of cytoplasmic and/or nuclear immunoreactivity was detected in 24/52 of the primary pNETs (46.2%) and in 16/27 of their liver metastases (59.3%). p-AKT1 expression was observed in 3 (21.4%) of NET grade (G) 1, in 14 (46.7%) of NET G2, and in 7 (87.5%) of NET G3. p-AKT1 expression was more frequently identified in pNET G3 category and increased during the tumor progression in metachronous liver metastases, as compared to the corresponding primary tumor. In addition, p-AKT1 positivity was significantly associated with an increase of grade from G1 to G3 (p = 0.004), the Ki-67 index (p = 0.029), the pTNM stage (p = 0.0008), perineural invasion (p = 0.031) and a decrease in disease-free survival (p = 0.05).Conclusion:The results suggest that p-АКТ1 plays an important role in the pathogenesis of pNETs and may be an additional criterion for assessment of the prognosis and treatment effectiveness in this type of tumors.

scholarly journals Prediction of Progression-Free Survival in Patients With Advanced, Well-Differentiated, Neuroendocrine Tumors Being Treated With a Somatostatin Analog: The GETNE-TRASGU Study

2019 ◽  
Vol 37 (28) ◽  
pp. 2571-2580 ◽  
Author(s):  
Alberto Carmona-Bayonas ◽  
Paula Jiménez-Fonseca ◽  
Ángela Lamarca ◽  
Jorge Barriuso ◽  
Ángel Castaño ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Failure Time ◽  
Somatostatin Analogs ◽  
Progression Free Survival ◽  
Accelerated Failure Time Model ◽  
Endocrine Tumors ◽  
First Line ◽  
Ki 67 ◽  
Free Survival ◽  
Well Differentiated

PURPOSE Somatostatin analogs (SSAs) are recommended for the first-line treatment of most patients with well-differentiated, gastroenteropancreatic (GEP) neuroendocrine tumors; however, benefit from treatment is heterogeneous. The aim of the current study was to develop and validate a progression-free survival (PFS) prediction model in SSA-treated patients. PATIENTS AND METHODS We extracted data from the Spanish Group of Neuroendocrine and Endocrine Tumors Registry (R-GETNE). Patient eligibility criteria included GEP primary, Ki-67 of 20% or less, and first-line SSA monotherapy for advanced disease. An accelerated failure time model was developed to predict PFS, which was represented as a nomogram and an online calculator. The nomogram was externally validated in an independent series of consecutive eligible patients (The Christie NHS Foundation Trust, Manchester, United Kingdom). RESULTS We recruited 535 patients (R-GETNE, n = 438; Manchester, n = 97). Median PFS and overall survival in the derivation cohort were 28.7 (95% CI, 23.8 to 31.1) and 85.9 months (95% CI, 71.5 to 96.7 months), respectively. Nine covariates significantly associated with PFS were primary tumor location, Ki-67 percentage, neutrophil-to-lymphocyte ratio, alkaline phosphatase, extent of liver involvement, presence of bone and peritoneal metastases, documented progression status, and the presence of symptoms when initiating SSA. The GETNE-TRASGU (Treated With Analog of Somatostatin in Gastroenteropancreatic and Unknown Primary NETs) model demonstrated suitable calibration, as well as fair discrimination ability with a C-index value of 0.714 (95% CI, 0.680 to 0.747) and 0.732 (95% CI, 0.658 to 0.806) in the derivation and validation series, respectively. CONCLUSION The GETNE-TRASGU evidence-based prognostic tool stratifies patients with GEP neuroendocrine tumors receiving SSA treatment according to their estimated PFS. This nomogram may be useful when stratifying patients with neuroendocrine tumors in future trials. Furthermore, it could be a valuable tool for making treatment decisions in daily clinical practice.

Are Cystic Pancreatic Neuroendocrine Tumors an Indolent Entity Results from a Single-Center Surgical Series

2017 ◽  
Vol 106 (3) ◽  
pp. 234-241 ◽  
Author(s):  
Salvatore Paiella ◽  
Giovanni Marchegiani ◽  
Marco Miotto ◽  
Anna Malpaga ◽  
Harmony Impellizzeri ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Survival Rates ◽  
Disease Free Survival ◽  
Postoperative Outcome ◽  
Tumor Diameter ◽  
Pancreatic Neuroendocrine Tumors ◽  
Ki 67 ◽  
Excellent Outcome ◽  
Comparison Results ◽  
Well Differentiated

Introduction: Cystic pancreatic neuroendocrine tumors (CPanNETs) represent an uncommon variant of pancreatic neuroendocrine tumors (PanNETs). Due to their rarity, there is a lack of knowledge with regard to clinical features and postoperative outcome. Methods: The prospectively maintained surgical database of a high-volume institution was queried, and 46 resected CPanNETs were detected from 1988 to 2015. Clinical, demographic, and pathological features and survival outcomes of CPanNETs were described and matched with a population of 92 solid PanNETs (SPanNETs) for comparison. Results: CPanNETs accounted for 7.8% of the overall number of resected PanNETs (46/587). CPanNETs were mostly sporadic (n = 42, 91%) and nonfunctioning (39%). Two functioning CPanNETs were detected (4.3%), and they were 2 gastrinomas. The median tumor diameter was 30 mm (range 10-120). All tumors were well differentiated, with 38 (82.6%) G1 and 8 (17.4%) G2 tumors. Overall, no CPanNET showed a Ki-67 >5%. A correct preoperative diagnosis of a CPanNET was made in half of the cases. After a median follow-up of >70 months, the 5- and 10-year overall survival of resected CPanNETs was 93.8 and 62.5%, respectively, compared to 92.7 and 84.6% for SPanNETs (p > 0.05). The 5- and 10-year disease-free survival rates were 94.5 and 88.2% for CPanNETs and 81.8 and 78.9% for SPanNETs, respectively (p > 0.05). Conclusion: In the setting of a surgical cohort, CPanNETs are rare, nonfunctional, and well-differentiated neoplasms. After surgical resection, they share the excellent outcome of their well-differentiated solid counterparts for both survival and recurrence.

Sporadic Gastric Well-Differentiated Neuroendocrine Tumors Have a Higher Ki-67 Proliferative Index

2016 ◽  
Vol 27 (3) ◽  
pp. 259-267 ◽  
Author(s):  
Hee Eun Lee ◽  
Taofic Mounajjed ◽  
Lori A. Erickson ◽  
Tsung-Teh Wu
Keyword(s):  
Neuroendocrine Tumors ◽  
Proliferative Index ◽  
Ki 67 ◽  
Well Differentiated

scholarly journals Albumin to alkaline phosphatase ratio: does it predict survival in grade 1 and grade 2 neuroendocrine tumors?

2019 ◽  
Author(s):  
Yusuf Acikgoz ◽  
Öznur Bal ◽  
Mutlu Doğan
Keyword(s):  
Alkaline Phosphatase ◽  
Neuroendocrine Tumors ◽  
Prognostic Value ◽  
Proliferation Index ◽  
Rank Test ◽  
P Value ◽  
Albumin Concentration ◽  
Ki 67 ◽  
Registration Data ◽  
Well Differentiated

Abstract BACKGROUND: Neuroendocrine tumors (NETs) are very heterogeneous tumors. Although it is classified according to Ki-67 proliferation index and mitotic count, their behavior may greatly vary even in the same group. Therefore, more accurate prognostic markers are required to predict prognosis in patients with well differentiated NETs. This study is aimed to evaluate prognostic value of albumin to alkaline phosphatase ratio (AAPR) in patients with well differentiated neuroendocrine tumors. PATIENTS AND METHODS: A total of 110 patients included in this study. Patients' data were obtained from registration data-base of the hospital and reviewed retrospectively. AAPR was calculated by dividing albumin concentration (g/dl) to alkaline phosphatase level (U/L). Cut off value for AAPR was determined by Receiver Operating Characteristic (ROC) analysis. Survival analysis was performed by Kaplan-Meier method with the Long-rank test. We reported two-sided p value and p<0.05 was considered statistically significant.RESULT: The calculated optimum cut-off value for AAPR was 0.028. Patients were divided into two groups as patients with AAPR ≤0.028 (n:22, 20%) and, with AAPR >0.028 (n:88, 80%). Patients with AAPR >0.028 had statistically longer overall survival (OS) compared with patients with ≤0.028 ( NR vs 96,8 months, p=0.001). Additionally, AAPR has been shown to be an independent prognostic factor for OS in in multivariate analysis (HR=4.942, 95% CI=1.693-14.420, p=0.003).CONCLUSION: Patients with higher AAPR had more favourable prognosis compared to patients with lower AAPR. We demonstrated that AAPR can be of prognostic value in well-differentiated NETs.

scholarly journals Neuroendocrine Tumors — Laboratory Diagnosis

2010 ◽  
Vol 29 (4) ◽  
pp. 254-264 ◽  
Author(s):  
Anna Tzontcheva
Keyword(s):  
Gastrointestinal Tract ◽  
Tumor Markers ◽  
Neuroendocrine Tumors ◽  
Chromogranin A ◽  
Endocrine Cells ◽  
Neuron Specific Enolase ◽  
Laboratory Diagnosis ◽  
Pancreatic Tumors ◽  
Endocrine Pancreatic Tumors ◽  
Well Differentiated

Neuroendocrine Tumors — Laboratory DiagnosisNeuroendocrine tumors (NETs) are a heterogeneous group of neoplasms originating from endocrine cells, which are characterized by the presence of secretory granules as well as the ability to produce biogenic amines and polypeptide hormones. These tumors originate from endocrine glands such as the adrenal medulla, the pituitary, and the parathyroids, as well as endocrine islets within the thyroid or the pancreas, and dispersed endocrine cells in the respiratory and gastrointestinal tract. The clinical behavior of NETs is extremely variable; they may be functioning or not functioning, ranging from very slow-growing tumors (well-differentiated NETs), which are the majority, to highly aggressive and very malignant tumors (poorly differentiated NETs). Classically, NETs of the gastrointestinal tract are classified into 2 main groups: (1) carcinoids and (2) endocrine pancreatic tumors (EPTs). Most neuroendocrine tumors produce and secrete a multitude of peptide hormones and amines. Some of these substances cause a specific clinical syndrome: carcinoid, Zollinger-Ellison, hyperglycemic, glucagonoma and WDHA syndrome. Specific markers for these syndromes are basal and/or stimulated levels of urinary 5-HIAA, serum or plasma gastrin, insulin, glucagon and vasoactive intestinal polypeptide, respectively. Some carcinoid tumors and about one third of endocrine pancreatic tumors do not present any clinical symptoms and are called ‘nonfunctioning’ tumors. Therefore, general tumor markers such as chromogranin A, pancreatic polypeptide, serum neuron-specific enolase and subunits of glycoprotein hormones have been used for screening purposes in patients without distinct clinical hormone-related symptoms. Among these general tumor markers chromogranin A, although its precise function is not yet established, has been shown to be a very sensitive and specific serum marker for various types of neuroendocrine tumors. This is because it may also be elevated in many cases of less well-differentiated tumors of neuroendocrine origin that do not secrete known hormones. At the moment, chromogranin A is considered the best general neuroendocrine serum or plasma marker available both for diagnosis and therapeutic evaluation, and is increased in 50-100% of patients with various neuroendocrine tumors. Chromogranin A serum or plasma levels reflect tumor load, and it may be an independent marker of prognosis in patients with midgut carcinoids.

Sign in / Sign up

Export Citation Format

Share Document