scholarly journals Chromogranin A, Ki-67 index and IGF-related genes in patients with neuroendocrine tumors

2013 ◽  
Vol 2 (4) ◽  
pp. 172-177 ◽  
Author(s):  
R C S van Adrichem ◽  
L J Hofland ◽  
R A Feelders ◽  
M C De Martino ◽  
P M van Koetsveld ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Neuroendocrine Tumors ◽  
Chromogranin A ◽  
Insulin Receptors ◽  
Proliferation Index ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Ki 67 ◽  
Igf Binding Proteins ◽  
Igf Receptors ◽  
Igf Binding

Chromogranin A (CgA) and the Ki-67 proliferation index are considered as important biochemical and pathological markers for clinical behaviour of gastroenteropancreatic neuroendocrine tumors (GEP NETs), respectively. The IGF system has been suggested as an important regulator of GEP NET proliferation and differentiation. A possible relationship between serum CgA (sCgA), Ki-67 proliferation index, and expression of IGF-related genes in patients with GEP NETs has not been demonstrated yet. This study investigates the relationship between sCgA, the Ki-67 proliferation index, and the expression of IGF-related genes in GEP NET tissues and their relation with 5-year survival. Tumor and blood samples from 22 GEP NET patients were studied. Tumoral mRNA expression of IGF-related genes (IGFs: IGF1, IGF2; IGF receptors: IGF1R, IGF2R; insulin receptors: subtype A (IR-A) and B (IR-B); IGF-binding proteins (IGFBPs): IGFBP1, IGFBP2, IGFBP3, and IGFBP6) was measured using quantitative RT-PCR. Ki-67 proliferation index was determined using immunohistochemistry. sCgA was measured with ELISA. Five-year survival in patients with nonelevated sCgA (n=11) was 91 vs 46% in patients with elevated sCgA (n=11) (P=0.006). IR-A mRNA expression was significantly higher in tumors obtained from patients with elevated sCgA than in those from patients with nonelevated sCgA (6.42±2.08 vs 2.60±0.40; P=0.04). This data suggests that sCgA correlates well with 5-year survival of GEP NET patients, and that IR-A mRNA expression correlates well with tumor mass in GEP NET patients.

Comparison of Monitor-Image and Printout-Image Methods in Ki-67 Scoring of Gastroenteropancreatic Neuroendocrine Tumors

2018 ◽  
Vol 30 (1) ◽  
pp. 17-23 ◽  
Author(s):  
Fatih Mert Dogukan ◽  
Banu Yilmaz Ozguven ◽  
Rabia Dogukan ◽  
Fevziye Kabukcuoglu
Keyword(s):  
Neuroendocrine Tumors ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Ki 67 ◽  
Monitor Image

Expression of IGFBP-2, -3, and -4 mRNA during differentiation of Caco-2 colon epithelial cells

1996 ◽  
Vol 271 (5) ◽  
pp. E922-E931 ◽  
Author(s):  
A. Hoeflich ◽  
Y. Yang ◽  
S. Huber ◽  
W. Rascher ◽  
G. Koepf ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Carcinoma Cell ◽  
Local Production ◽  
Igf Binding Proteins ◽  
Colon Carcinoma Cell Line ◽  
Long Term Culture ◽  
Protein Levels ◽  
Igf Binding ◽  
Igfbp 3

Local production of insulin-like growth factor (IGF)-binding proteins (IGFBP) determines the availability of the IGF to the cell and thus regulates IGF action. To find out whether specific patterns of IGFBP gene expression and IGFBP secretion were related to cell growth vs. cell differentiation, expression of IGFBP during long-term culture (21 days, n = 5) of the colon carcinoma cell line Caco-2 was investigated at the mRNA and protein levels. Markers of cell proliferation (increase in DNA, RNA, and protein content) and of differentiation [alkaline phosphatase (AP) activity; creatine kinase (CK) activity] were measured in parallel during long-term culture. IGFBP-2 mRNA expression correlated significantly with markers of proliferation (P < 0.05), whereas IGFBP-3 mRNA expression or IGFBP-3 secretion correlated with markers of differentiation (AP: r = 0.83, P < 0.001; CK: r = 0.45, P < 0.01). Similarly, IGFBP-4 mRNA expression correlated significantly with markers of differentiation (AP: r = 0.34, P < 0.05; CK: r = 0.35, P < 0.05). We hypothesize that IGFBP-3 and -4 are related to differentiation of Caco-2 cells, whereas IGFBP-2 is related to proliferation in Caco-2 cells.

IGF-II, IGF-binding proteins and IGF receptors in pancreatic β-cell lines

1997 ◽  
Vol 152 (3) ◽  
pp. 455-464 ◽  
Author(s):  
L E L Katz ◽  
A Bhala ◽  
E Camron ◽  
S E Nunn ◽  
R L Hintz ◽  
...  
Keyword(s):  
Cell Lines ◽  
Binding Proteins ◽  
Conditioned Media ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Igf Binding Proteins ◽  
Igf Receptors ◽  
Igf I ◽  
Igf Binding ◽  
Hit Cells

The IGFs are mitogenic agents which are closely linked to regulatory processes in carbohydrate metabolism. Because limited information is available on the occurrence of the IGF system in the pancreatic β-cell milieu, we evaluated the presence of IGFs, IGF receptors, and IGF-binding proteins (IGFBPs) in the β-cell lines βTC3 and HIT T-15. Serum-free conditioned media (SFCM) from βTC3 cells contained IGF-II at concentrations greater than 100 ng/ml. High (15 kDa) and low (7·5 kDa) molecular weight IGF-II were detected both by column chromatography followed by RIA and by immunoblotting. GH (10–1000 ng/ml) conditioning of βTC3 cells stimulated IGF-II secretion in a dose-dependent manner. IGF-II mRNA was detected in βTC3 cells using Northern blots, and also showed a GH-dependent relationship. IGF-II peptide was detected in SFCM from HIT cells, albeit at lower concentrations. To evaluate the presence of IGF receptors in β-cell lines, affinity cross-linking studies were performed on βTC3 cells, demonstrating type I IGF receptors which bound iodinated IGF-II with high affinity, iodinated IGF-I with lesser affinity, and had minimal appreciable binding to iodinated insulin. Type II IGF receptors were not detected. SFCM from βTC3 and HIT cells was subjected to Western ligand blotting, which disclosed the presence of two major IGFBPs of 29 kDa and 24 kDa, characteristic of IGFBP-2 and IGFBP-4. The identity of the specific IGFBPs was confirmed by immunoprecipitation and Northern blotting. Varying the glucose concentration had no significant effect on the levels of IGFBPs, nor did preconditioning with GH, IGF-I, IGF-II, insulin, or glucagon. Levels of both IGFBPs in βTC3 cell-conditioned media increased in the presence of dexamethasone at concentrations of 10−6 m or greater. In summary, we present evidence that β-cell lines comprise an environment for GH and IGF action. We speculate that IGFs, their receptors and binding proteins function as a complex interactive system which regulates β-cell growth and function. Journal of Endocrinology (1997) 152, 455–464

Evaluation of gastroenteropancreatic neuroendocrine tumors for Ki 67, p16 and cyclin D1 expression

2011 ◽  
Vol 12 (3) ◽  
pp. 105-112
Author(s):  
Gulzade Ozyalvacli ◽  
Esra Pasaoglu ◽  
Zuhal Gucin ◽  
Kemal Behzatoglu ◽  
Feray Gunver ◽  
...  
Keyword(s):  
Cyclin D1 ◽  
Neuroendocrine Tumors ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Ki 67

STAT3 inhibition for gastroenteropancreatic neuroendocrine tumors: Potential for a new therapeutic target?

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 340-340
Author(s):  
Alexandra G Lopez-Aguiar ◽  
Lauren McLendon Postlewait ◽  
Mohammad Zaidi ◽  
Kristen Zhelnin ◽  
Alyssa Krasinskas ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Lymphovascular Invasion ◽  
Therapeutic Option ◽  
Microvascular Density ◽  
Vascular Tumors ◽  
Vegf Expression ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Ki 67 ◽  
Low Expression ◽  
Stat3 Inhibition

340 Background: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are highly vascular tumors with similar treatments applied to all sites. The expression of pro-angiogenic factors (STAT3, VEGF, and HIF-1α) and their association with known adverse pathologic factors and disease recurrence after resection is not known. Methods: All pts with non-metastatic primary GEP-NETs who underwent curative-intent resection at a single institution from 2000-2013 were included. Immunohistochemistry was performed for STAT3, VEGF, HIF-1α, Ki-67 index, and CD31 using tissue microarrays made in triplicate by a pathologist blinded to other clinicopathologic variables. STAT3, VEGF, and HIF-1α were categorized into high vs low expression; CD31 was dichotomized at the median value. Primary outcome was 3-yr recurrence-free survival (3-yr RFS); secondary outcomes were correlation of STAT3, VEGF, and HIF-1α expression with Ki-67 index, adverse pathologic factors, and CD31 expression, a marker of microvascular density. Results: Of 265 GEP-NETs resected, 144 had tissue for analysis. STAT3 expression was high in 12 (8%) and low in 132 (92%). VEGF expression was high in 19 (13%) and low in 125 (87%), and HIF-1α was high in 1 (1%) and low in 143 (99%). High STAT3 expression was associated with worse 3-yr RFS compared to low expression (55% vs 84%; p = 0.003). High VEGF expression had a 3-yr RFS of 76% compared to 82% for low expression (p = 0.098); HIF-1α expression was not associated with RFS. Ki-67 ≥3% was associated with worse 3-yr RFS (≥3%: 51% vs < 3%: 84%; p < 0.001), as was the presence of lymphovascular invasion (LVI: 72% vs 95%; p = 0.001) and increased microvascular density per µm2 (CD31 > median: 75% vs CD31 < median: 86%; p = 0.043). High STAT3 expressing tumors were more likely to have a Ki-67≥3% (42% vs 7%; p < 0.001). LVI was present in 82% of high STAT3 tumors compared to only 50% with low STAT3 (p = 0.058). CD31 overexpression was similar between groups (58% vs 49%; p = 0.5). Conclusions: In resected GEP-NETs, high STAT3 expression is associated with an increased Ki-67 index, presence of lymphovascular invasion, and worse 3-yr RFS. STAT3 inhibition may be a novel therapeutic option for patients undergoing resection of high-risk tumors.

Canine Neuroendocrine Tumors of the Pancreas: A Study Using Image Analysis Techniques for the Discrimination of Metastatic Versus Nonmetastatic Tumors

1997 ◽  
Vol 34 (2) ◽  
pp. 138-145 ◽  
Author(s):  
G. Minkus ◽  
U. Jütting ◽  
M. Aubele ◽  
K. Rodenacker ◽  
P. Gais ◽  
...  
Keyword(s):  
Image Analysis ◽  
Neuroendocrine Tumors ◽  
Nucleolar Organizer ◽  
Biological Behavior ◽  
Proliferation Index ◽  
Nucleolar Organizer Regions ◽  
Ki 67 ◽  
Analysis Techniques ◽  
Significant Difference ◽  
Image Analysis Techniques

Canine pancreatic neuroendocrine tumors were studied using different image analysis techniques (nuclear image histometry, analysis of argyrophilic proteins of nucleolar organizer regions, determination of the mouse anti-Ki 67 antigen proliferation index, and DNA densitometry) to correlate their biological behavior with objective phenotypic markers. The methods were compared to determine the best method for distinguishing between metastatic and nonmetastatic tumors. Discrimination between the two types of tumor was possible using nuclear image histometry in combination with morphometric analysis of argyrophilic proteins of nucleolar organizer regions. In contrast, the mouse anti-Ki 67 antigen proliferation index, DNA measurement, and immunohistochemical parameters revealed no significant difference between the two types of tumors.

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