Can malignancy in insulinoma be predicted by the expression patterns of beta 1,6 branching of asparagine-linked oligosaccharides and polysialic acid of the neural cell adhesion molecule?
Abstract:We analysed the value of the expression of beta 1,6 branching of asparagine-linked oligosaccharide chains and polysialic acid of the neural cell adhesion molecule (NCAM) in predicting malignant behaviour in human insulinomas, as these glycoconjugates have been associated with invasive growth and metastatic potential. Fifty-three insulinomas from patients with well-documented clinical and follow-up data were investigated. Lectin histochemical staining for beta 1,6 branches revealed that 11 (74%) of the 15 malig… Show more
“…Polysialylated NCAM was not detectable in insulinomas, and the NCAM protein isoform pattern was similar in benign and malignant tumors. Furthermore, 74% of the malignant and 63% of the benign tumors exhibited staining for beta-1,6branches [99]. The most widely observed alteration in cell-to-environment interactions in cancer involves E-cadherin, a homotypic cell-to-cell interaction molecule ubiquitously expressed on epithelial cells [1].…”
Insulinomas are the most common functioning endocrine pancreatic tumors (EPTs). They present with clinical symptoms as a consequence of hypoglycemia induced by inappropriate insulin secretion. The etiology of these tumors is poorly understood. Some tumors may harbor MEN1 gene mutations, the susceptibility gene of the multiple endocrine neoplasia type I syndrome, but most cases show wildtype MEN1. Currently, no reliable clinical tests are available to differentiate benign from malignant tumors. Approximately 30% of the tumors are unresectable, and they often show different growth rates, which hampers treatment. Therefore, a better understanding of the molecular processes underlying the development and progression of insulinomas is required to improve diagnosis, prognosis and therapy. Here we summarize the progress that has been made in insulinoma research in the past decade. We describe the clinical detection, classification and treatment of these tumors, and review the multiplicity of molecular and genetic studies that investigated tumor development and progression using either primary tumors, transgenic mouse models or tumor-derived cell lines. The identification of many interactors of the MEN1 gene product menin, as well as recurrent chromosomal abnormalities that pinpoint candidate genes of interest will likely result in a better understanding of the molecular pathways involved in insulinoma tumorigenesis. In addition, these studies will pave the way for the identification of novel targets for therapeutical intervention and more reliable markers for clinical diagnosis and prognosis.
“…Polysialylated NCAM was not detectable in insulinomas, and the NCAM protein isoform pattern was similar in benign and malignant tumors. Furthermore, 74% of the malignant and 63% of the benign tumors exhibited staining for beta-1,6branches [99]. The most widely observed alteration in cell-to-environment interactions in cancer involves E-cadherin, a homotypic cell-to-cell interaction molecule ubiquitously expressed on epithelial cells [1].…”
Insulinomas are the most common functioning endocrine pancreatic tumors (EPTs). They present with clinical symptoms as a consequence of hypoglycemia induced by inappropriate insulin secretion. The etiology of these tumors is poorly understood. Some tumors may harbor MEN1 gene mutations, the susceptibility gene of the multiple endocrine neoplasia type I syndrome, but most cases show wildtype MEN1. Currently, no reliable clinical tests are available to differentiate benign from malignant tumors. Approximately 30% of the tumors are unresectable, and they often show different growth rates, which hampers treatment. Therefore, a better understanding of the molecular processes underlying the development and progression of insulinomas is required to improve diagnosis, prognosis and therapy. Here we summarize the progress that has been made in insulinoma research in the past decade. We describe the clinical detection, classification and treatment of these tumors, and review the multiplicity of molecular and genetic studies that investigated tumor development and progression using either primary tumors, transgenic mouse models or tumor-derived cell lines. The identification of many interactors of the MEN1 gene product menin, as well as recurrent chromosomal abnormalities that pinpoint candidate genes of interest will likely result in a better understanding of the molecular pathways involved in insulinoma tumorigenesis. In addition, these studies will pave the way for the identification of novel targets for therapeutical intervention and more reliable markers for clinical diagnosis and prognosis.
“…For example, all epithelia along the gastrointestinal tract were positive, with the exception of those of the colonic mucosa. Furthermore, epithelia of nonlactating breast were unreactive, but studies in human breast carcinoma with regard to the prognostic value of β1,6-branched oligosaccharides produced contradictory results. , Studies performed on insulinomas and melanomas also failed to establish a correlation with malignancy and metastasis. 12 Histochemical demonstration of β1,6-branched oligosaccharides with the leukoagglutinating Phaseolus vulgaris lectin.…”
Section: 21 β16-branched Oligosaccharides Tumor
Progression and Metas...mentioning
confidence: 99%
“…In the thyroid gland, medullary but no other type of carcinoma expressed polysialic acid, in the adrenal gland, pheochromocytoma but not adrenocortical carcinoma, and in lung small cell carcinoma but not so-called carcinoid. In benign and malignant insulinoma, polysialic acid was undetectable, despite the presence of NCAM 14 Immunohistochemical demonstration with a monoclonal antibody of polysialic acid of the neural cell adhesion molecule in human kidney.…”
Section: 23 Polysialic Acid Of the Neural Cell Adhesion
Moleculementioning
“…In breast carcinoma a negative association between L-PHA histochemical staining in the tumor and the presence of axillary lymph node metastases has been reported (Chammas et al, 1994); similar results were reported in experimental models. Furthermore, our recent L-PHA histochemical studies in human insulinomas revealed no association between staining for beta 1,6 branches and malignancy or metastasis in this neuroendocrine pancreatic tumor (Li et al, 1996). Collectively, these results indicate that L-PHA histochemistry may not be a generally applicable technique in tumor diagnosis and staging and may have limited value as a prognostic indicator.…”
Malignant transformation of cells leads to the synthesis of large asparagine-linked oligosaccharides that exhibit a higher degree of beta 1,6 branching. In rodent and human tumor cell lines and certain human tumors, increased beta 1,6 branching of oligosaccharides has been shown to be associated with metastasis. In addition, this structural change occurs in glycoproteins of stimulated normal human lymphocytes. The leukoagglutinating Phaseolus vulgaris lectin (L-PHA) has a high affinity for tri-and tetraantennary beta 1,6 branches carrying oligosaccharides and has been widely used for the detection of such structures by histochemistry and blotting. We have analyzed a spectrum of normal human and rat tissues using a sensitive silver-intensified lectin-gold technique. Staining by L-PHA was detected in undifferentiated cells of germinative layers of the gastrointestinal and respiratory tract as well as testis. However, differentiated and non-mitotic epithelia in most organs showed strong lectin staining as well. Notable exceptions were the epithelium of the colon and resting mammary gland, which were unreactive with L-PHA. The histochemical studies were supplemented by lectin blotting, which showed the presence of diverse L-PHA-reactive glycoproteins in rat tissues. Our data may be of importance for the use of L-PHA in studies on human malignant tumors. Int.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
