Cleaved caspase-3 immunocytochemical staining for pancreatic islets and pancreatic endocrine tumors: A potential marker for biological malignancy

Tomita, Tatsuo

doi:10.4161/isl.2.2.10807

Cited by 10 publications

(6 citation statements)

References 17 publications

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“…Among non-β-cell PETs, 2 of 2 glucagonomas (100%), 6 of 9 pancreatic polypeptidomas (67%), 10 of 12 gastrinomas (83%), and 3 of 3 non-functioning PETs (100%) were negative for cleaved caspase-3 immunostaining at a total of 21 of 24 non-β-cell tumors (88%) being negative. These results support that 88% of non-β-cell PETs are potentially malignant by the absence of cleaved caspase-3 immunostaining [38] and that negative cleaved caspase-3 immunostaining may be a candidate of malignant marker for PETs [38]. So far, positive activated caspase-3 immunostaining appears to be a good marker for β-cell apoptosis.…”

Section: Apoptosis In Pancreatic β-Cells By the Immunologic And Immunsupporting

confidence: 76%

“…We agree with Duan et al that cleaved caspase-3 immunostaining is an easier and more reliable immunostaining than TUNEL, although the former is not as commonly used as the latter. Cleaved caspase-3 immunostaining has also its own pitfalls as for the immunostaining staining in general: Good fixation with an optimal tissue preservation and proper tissue processing are essential using an adequate concentration of antibody for optimal cleaved caspase-3 immunostaining and the stained sections have to be critically evaluated for discernible nuclear positive staining by excluding false-positive staining in tissue debris and autolytic tissues [22,[36][37][38].…”

Section: Apoptosis In Pancreatic β-Cells By the Immunologic And Immunmentioning

confidence: 99%

“…Our group studied cleaved caspase-3 immunostaining in 37 cases of pancreatic endocrine tumors (PETs) [38]: Among 15 cases of insulinomas, five cases were positive, and 10 cases were negative for cleaved caspase-3 (67%). Among non-β-cell PETs, 2 of 2 glucagonomas (100%), 6 of 9 pancreatic polypeptidomas (67%), 10 of 12 gastrinomas (83%), and 3 of 3 non-functioning PETs (100%) were negative for cleaved caspase-3 immunostaining at a total of 21 of 24 non-β-cell tumors (88%) being negative.…”

Section: Apoptosis In Pancreatic β-Cells By the Immunologic And Immunmentioning

confidence: 99%

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Apoptosis in pancreatic β-islet cells in Type 2 diabetes

Tomita

2016

Bosn J of Basic Med Sci

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160

116

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Apoptosis plays important roles in the pathophysiology of Type 2 diabetes mellitus (T2DM). The etiology of T2DM is multifactorial, including obesity-associated insulin resistance, defective insulin secretion, and loss of β-cell mass through β-cell apoptosis. β-cell apoptosis is mediated through a milliard of caspase family cascade machinery in T2DM. The glucose-induced insulin secretion is the principle pathophysiology of diabetes and insufficient insulin secretion results in chronic hyperglycemia, diabetes. Recently, hyperglycemia-induced β-cell apoptosis has been extensively studied on the balance of pro-apoptotic Bcl-2 proteins (Bad, Bid, Bik, and Bax) and anti-apoptotic Bcl family (Bcl-2 and Bcl-xL) toward apoptosis in vitro isolated islets and insulinoma cell culture. Apoptosis can only occur when the concentration of pro-apoptotic Bcl-2 exceeds that of anti-apoptotic proteins at the mitochondrial membrane of the intrinsic pathway. A bulk of recent research on hyperglycemia-induced apoptosis on β-cells unveiled complex details on glucose toxicity on β-cells in molecular levels coupled with cell membrane potential by adenosine triphosphate generation through K+ channel closure, opening Ca2+ channel and plasma membrane depolarization. Furthermore, animal models using knockout mice will shed light on the basic understanding of the pathophysiology of diabetes as a glucose metabolic disease complex, on the balance of anti-apoptotic Bcl family and pro-apoptotic genes. The cumulative knowledge will provide a better understanding of glucose metabolism at a molecular level and will lead to eventual prevention and therapeutic application for T2DM with improving medications.

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Section: Apoptosis In Pancreatic β-Cells By the Immunologic And Immunsupporting

confidence: 76%

Section: Apoptosis In Pancreatic β-Cells By the Immunologic And Immunmentioning

confidence: 99%

Section: Apoptosis In Pancreatic β-Cells By the Immunologic And Immunmentioning

confidence: 99%

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Apoptosis in pancreatic β-islet cells in Type 2 diabetes

Tomita

2016

Bosn J of Basic Med Sci

Self Cite

160

116

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“…This mechanism conditions normal cell function and enables maintenance of homeostasis (7). The process of apoptosis involves the Bcl-2 family-dependent signaling pathway and the caspase-regulated signaling pathway (7).…”

Section: Discussionmentioning

confidence: 99%

Reduced expression of caspase-8 and cleaved caspase-3 in pancreatic ductal adenocarcinoma cells

et al. 2016

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Abstract. Pancreatic ductal adenocarcinoma (PDAC) is a rare neoplasm that affects the gastrointestinal system, and is characterized by a high mortality rate. It has been demonstrated that apoptosis has a significant role in the regulation of cancer cells. Therefore, the aim of the present study was to immunohistochemically assess the expression of proteins belonging to the caspase family, namely caspase-8, pro-caspase-3 and cleaved (active) caspase-3 in pancreatic cancer. The study group consisted of 29 patients exhibiting PDAC. Protein expression was evaluated by immunohistochemical methods. The expression of caspase-8 in normal cells was negative in 17.2% of cases and positive in 82.8% of cases. All cases demonstrated pro-caspase-3 expression in normal pancreatic cells, compared with 93.1% of cancer cells. Staining for activated caspase-3 was positive in 27 normal tissue cases, compared with positivity in only 10 cancer cases. Caspase-8 expression positively correlated with cleaved caspase-3 expression in the cytoplasm of cancer cells (P<0.002). Caspase-3 expression was identified to correlate with inflammatory peritumoral infiltration (P<0.015). No correlation was observed between caspase expression and any other clinicopathological parameters. The results of the present study demonstrated aberrant initiation of cancer cell apoptosis in PDAC via a decrease in caspase-8 expression, which may lead to disorders in the activation of effector caspase-3.

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“…(11) Higher expression of the apoptosis related protein, cleaved-caspase 3 (CC3), has been associated with prognosis in PNETs with greater expression in benign PNETs as compared to malignant sporadic PNETs. (12) The expression of vascular endothelial growth factor (VEGF) has been associated with tumor aggressiveness and patient prognosis in a variety of human malignancies. (13) Lastly, altered p53 expression is frequently seen in many tumors, with TP53 cited as the most frequently mutated gene associated with malignancy.…”

Section: Introductionmentioning

confidence: 99%

Altered PTEN, ATRX, CHGA, CHGB, and TP53 Expression Are Associated with Aggressive VHL-Associated Pancreatic Neuroendocrine Tumors

et al. 2013

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Von Hippel-Lindau (VHL) syndrome is an inherited cancer syndrome in which 8-17% of germline mutation carriers develop pancreatic neuroendocrine tumors (PNETs). There is limited data on prognostic markers for PNETs other than Ki-67, which is included in the World Health Organization classification system. Recently, specific genes and pathways have been identified by whole exome sequencing which may be involved in the tumorigenesis of PNETs and may be markers of disease aggressiveness. The objective of this study was to identify molecular markers of aggressive disease in VHL-associated PNETs. The protein expression of 8 genes (PTEN, CHGA, CHGB, ATRX, DAXX, CC-3, VEGF, TP53) was analyzed in PNETs by immunohistochemistry and compared to clinical data, VHL genotype, functional imaging results, and pathologic findings. Subcellular distribution of PTEN, CHGA and ATRX were significantly different by WHO classifications (p<0.05). There was decreased PTEN nuclear to cytoplasmic ratio (p<0.01) and decreased CHGA nuclear expression (p=0.03) in malignant samples as compared to benign. Lower cytoplasmic CHGB expression (p=0.03) was associated with malignant tumors and metastasis. Higher nuclear expression of PTEN was associated with VHL mutations in exon 3 (p=0.04). Higher PTEN and CHGB expression was associated with higher FDG-PET avidity (p<0.05). Cytoplasmic expression of CC-3 was associated with higher serum Chromogranin A levels (σ=0.72, p= 0.02). Lastly, greater cytoplasmic expression of p53 was associated with metastasis. Our findings suggest that altered PTEN, ATRX, CHGA and CHGB expression are associated with aggressive PNET phenotype in VHL and may serve as useful adjunct prognostic markers to Ki-67 in PNETs.

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Cleaved caspase-3 immunocytochemical staining for pancreatic islets and pancreatic endocrine tumors: A potential marker for biological malignancy

Abstract: To cite this article: Tatsuo Tomita (2010) Cleaved caspase-3 immunocytochemical staining for pancreatic islets and pancreatic endocrine tumors: A potential marker for biological malignancy, Islets, 2:2, 82-88,

Cited by 10 publications

References 17 publications

Apoptosis in pancreatic β-islet cells in Type 2 diabetes

Apoptosis in pancreatic β-islet cells in Type 2 diabetes

Reduced expression of caspase-8 and cleaved caspase-3 in pancreatic ductal adenocarcinoma cells

Altered PTEN, ATRX, CHGA, CHGB, and TP53 Expression Are Associated with Aggressive VHL-Associated Pancreatic Neuroendocrine Tumors

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