Measurement of Interobserver Variability in Calculating MIB1 Labeling Index By Counting Tumor Cells in Well Differentiated Neuroendocrine Tumors (WDNETs) of the Pancreas and Gastrointestinal Tract : A Cytologic Analysis of 22 Cases

2012 ◽  
Vol 1 (1) ◽  
pp. S95 ◽  
Author(s):  
Adele Fung ◽  
Cynthia Cohen ◽  
Sravankumar Kavuri ◽  
XIn Gao ◽  
Michelle Reid
Keyword(s):  
Gastrointestinal Tract ◽  
Tumor Cells ◽  
Neuroendocrine Tumors ◽  
Interobserver Variability ◽  
Labeling Index ◽  
Cytologic Analysis ◽  
Well Differentiated

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.

Uniform and Robust Nuclear Expression of HES1 in Neuroendocrine Neoplasms

2019 ◽  
Vol 27 (8) ◽  
pp. 844-851
Author(s):  
Min Cui ◽  
Zhenjian Cai ◽  
Amad Awadallah ◽  
Wei Xin
Keyword(s):  
Gastrointestinal Tract ◽  
Neuroendocrine Tumors ◽  
Notch Signaling Pathway ◽  
Neuroendocrine Neoplasms ◽  
Nuclear Staining ◽  
Typical Carcinoid ◽  
Downstream Target ◽  
Nuclear Expression ◽  
Hes1 Expression ◽  
Well Differentiated

Introduction. Neuroendocrine neoplasms (NENs) are neoplasms that most commonly arise from gastrointestinal tract, pancreas, and lung. HES1 is a downstream target of Notch signaling pathway. The current literature about HES1 expression in NENs is sparse and inconsistent. Methods. In this study, we evaluated HES1 expression by immunohistochemistry in a total of 32 cases of NENs, including 13 well-differentiated neuroendocrine tumors from gastrointestinal tract, 10 cases of well-differentiated neuroendocrine tumors of pancreas, 9 cases from lung, including 4 cases of typical carcinoid, 1 case of atypical carcinoid, and 4 cases of neuroendocrine carcinoma. The intensity of the stain was scored from − to +++, and the distribution of the staining of HES1 was evaluated. Results. HES1 demonstrates uniform robust (+++) nuclear staining pattern in the tumor cells of all the NENs (32/32), regardless of the origin of the system and the grade of the tumor. Conclusions. HES1 is uniformly expressed in NENs with robust nuclear expression pattern. Our finding suggests that NOTCH1 or HES1 inhibitor is a potential therapeutic choice for neuroendocrine neoplasms.

In vitro chemotherapy profiling of well-differentiated midgut neuroendocrine tumors (NETs) based on individual patient tumor biomarkers analysis.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 235-235
Author(s):  
Yi-Zarn Wang ◽  
Jean P. Carrasquillo ◽  
Alexis Carimi ◽  
Elizabeth McCord ◽  
Maria M. Chester ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Tumor Cells ◽  
Neuroendocrine Tumors ◽  
Tumor Biomarker ◽  
Primary Tumors ◽  
Sensitivity Assessment ◽  
Biomarker Analysis ◽  
Well Differentiated

235 Background: Midgut neuroendocrine tumors (NETs) are rare malignancies with indolent clinical courses. In general, they are well differentiated with most tumor cells in the G0 phase of the cell cycle, consistent with the poor response rate of NETs to chemotherapy in vivo. We hypothesize that insults, such as surgery, can drive NET cells from G0 into S phase and that biomarker analysis of individual patient tumors harvested and grown in the lab will provide useful practical guide for future intra and post operative adjuvant therapy. Methods: 97 well-differentiated midgut NET patients underwent cytoreductive surgery at our institution between 5/2012 and 10/2012. 148 surgical specimens were collected and submitted to a single commercial lab for processing. Primary tumors, lymph nodes and liver metastases were harvested and cultured. Their RNAs were then extracted to analyze the expressivity a total of 88 different biomarkers. Based on our patients specific tumor biomarker expressivity and known correlations between 36 anti-neoplastic agents with their linked biomarkers, recommendations were reported as clinically benefit or lacking such benefit. Results: A total of 148 specimens from 97 patients were tested. In four of the 97 patients, no clinically beneficial chemotherapy agent could be identified. Among the remaining 93 patients, the top three agents that are most likely to be clinically beneficial are: Fluorouracil, Cisplatin and Carboplatin. These were reported to be clinically beneficial in 135/148 (91.2%), 103/148 (69.6%), and 103/148 (69.6%) patients respectively. Conclusions: Midgut NETs are slow growing tumors which are chemotherapeutically inert owing to the fact that most of the tumor cells are in G0 cell cycle. Surgical insult drives NET cells into active synthetic phase where they begin to express biomarkers specific to their tumor cells. Analysis of these biomarkers guides further potential beneficial therapy based on the current known associations among biomarkers and chemotherapy agents. These results must then be compared and confirmed against a direct in-vitro chemo sensitivity assessment conducted simultaneously on the same patients.

scholarly journals Prospective study of dynamic whole-body 68Ga-DOTATOC-PET/CT acquisition in patients with well-differentiated neuroendocrine tumors

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Philippe Thuillier ◽  
David Bourhis ◽  
Jean Philippe Metges ◽  
Romain Le Pennec ◽  
Karim Amrane ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Linear Relation ◽  
Whole Body ◽  
Pet Ct ◽  
Non Linear ◽  
Well Differentiated ◽  
Analog Systems ◽  
Pet System ◽  
Dynamic Acquisition ◽  
Linear Regressions

AbstractTo present the feasibility of a dynamic whole-body (DWB) 68Ga-DOTATOC-PET/CT acquisition in patients with well-differentiated neuroendocrine tumors (WD-NETs). Sixty-one patients who underwent a DWB 68Ga-DOTATOC-PET/CT for a histologically proven/highly suspected WD-NET were prospectively included. The acquisition consisted in single-bed dynamic acquisition centered on the heart, followed by the DWB and static acquisitions. For liver, spleen and tumor (1–5/patient), Ki values (in ml/min/100 ml) were calculated according to Patlak's analysis and tumor-to-liver (TLR-Ki) and tumor-to-spleen ratios (TSR-Ki) were recorded. Ki-based parameters were compared to static parameters (SUVmax/SUVmean, TLR/TSRmean, according to liver/spleen SUVmean), in the whole-cohort and according to the PET system (analog/digital). A correlation analysis between SUVmean/Ki was performed using linear and non-linear regressions. Ki-liver was not influenced by the PET system used, unlike SUVmax/SUVmean. The regression analysis showed a non-linear relation between Ki/SUVmean (R2 = 0.55,0.68 and 0.71 for liver, spleen and tumor uptake, respectively) and a linear relation between TLRmean/TLR-Ki (R2 = 0.75). These results were not affected by the PET system, on the contrary of the relation between TSRmean/TSR-Ki (R2 = 0.94 and 0.73 using linear and non-linear regressions in digital and analog systems, respectively). Our study is the first showing the feasibility of a DWB 68Ga-DOTATOC-PET/CT acquisition in WD-NETs.

scholarly journals Recent Updates on Neuroendocrine Tumors From the Gastrointestinal and Pancreatobiliary Tracts

2016 ◽  
Vol 140 (5) ◽  
pp. 437-448 ◽  
Author(s):  
Joo Young Kim ◽  
Seung-Mo Hong
Keyword(s):  
World Health Organization ◽  
Neuroendocrine Tumors ◽  
Classification Scheme ◽  
Neuroendocrine Cells ◽  
Labeling Index ◽  
World Health ◽  
World Health Organization Classification ◽  
Clinicopathologic Characteristics ◽  
Ki 67 ◽  
Health Organization

Context.—Gastrointestinal (GI) and pancreatobiliary tracts contain a variety of neuroendocrine cells that constitute a diffuse endocrine system. Neuroendocrine tumors (NETs) from these organs are heterogeneous tumors with diverse clinical behaviors. Recent improvements in the understanding of NETs from the GI and pancreatobiliary tracts have led to more-refined definitions of the clinicopathologic characteristics of these tumors. Under the 2010 World Health Organization classification scheme, NETs are classified as grade (G) 1 NETs, G2 NETs, neuroendocrine carcinomas, and mixed adenoneuroendocrine carcinomas. Histologic grades are dependent on mitotic counts and the Ki-67 labeling index. Several new issues arose after implementation of the 2010 World Health Organization classification scheme, such as issues with well-differentiated NETs with G3 Ki-67 labeling index and the evaluation of mitotic counts and Ki-67 labeling. Hereditary syndromes, including multiple endocrine neoplasia type 1 syndrome, von Hippel-Lindau syndrome, neurofibromatosis 1, and tuberous sclerosis, are related to NETs of the GI and pancreatobiliary tracts. Several prognostic markers of GI and pancreatobiliary tract NETs have been introduced, but many of them require further validation. Objective.—To understand clinicopathologic characteristics of NETs from the GI and pancreatobiliary tracts. Data Sources.—PubMed (US National Library of Medicine) reports were reviewed. Conclusions.—In this review, we briefly summarize recent developments and issues related to NETs of the GI and pancreatobiliary tracts.

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