Pancreatitis endocrine

Bergmann F, Breinig M, Hopfner M, et al. Expression pattern and functional relevance of epidermal growth factor receptor and cyclooxygenase-2 novel chemotherapeutic targets in pancreatic endocrine tumors. Am. J. Gastroenterol. 2009 104 171-181. 

Meschi F, di Natale B, Rondanini GF, Uderzo C, Jankovic M, Masera G, Chiumello G. Pancreatic endocrine function in leukemic children treated with L-aspar-aginase. Horm Res 1981 15(4) 237-41. 

O Keefe SJD, Cariem AK, Levy M. The exacerbation of pancreatic endocrine dysfunction by potent pancreatic exocrine supplements in patients with chronic pancreatitis. J Clin Gastroenterol 2001 32 319-23. 

Schulte-Frohlinde, E., Schmid, R., Brand, V., and Schusdziarra, V. 1994. Effect of bovine (3-casomorphin-4-amide on gastrointestinal transit and pancreatic endocrine function in man. In (3-Casomorphins and Related Peptides Recent Developments (V. Brand and H. Teschemacher, eds), pp. 155—160. VCH, Weinheim. 

Jacobsson G, Bean AJ, Scheller RH, Juntti-Berggren L, Beeney JT, Berggren PO, Meis-ter B (1994) Identification of synaptic proteins and their isoform mRNA in compartments of pancreatic endocrine cells. In Proc. Natl. Acad. Sci. USA 91 12487-91 Jancovic J, Hallett M (eds) (1994) Therapy with botulinum toxin. New York Marcel Dekker... 

Demeterco C, Itkin-Ansari P, Tyrberg B, et al. c-Myc controls proliferation versus differentiation in human pancreatic endocrine cells. / Clin Endocrinol Metab. 2002 87(7) 3475—3485. 

Enolase is a glycolytic enzyme also known as phosphopyru-vate hydratase. Neuron-specific enolase (NSE) is the form of enolase found in neuronal tissue and in the cells of the diffuse neuroendocrine system and the amine precursor uptake, and decarboxylation (APUD) tissue. NSE is found in tumors associated with the neuroendocrine origin, including small cell lung cancer (SCLC), neuroblastoma, pheochromocytoma, carcinoid, medullary carcinoma of the thyroid, melanoma, and pancreatic endocrine tumors. 

Lloyd RV, Mervak T, Schmidt K, et al. Immunohistochemical detection of chromogranin and neuron-specific enolase in pancreatic endocrine neoplasms. Am J Surg Pathol. 1984 8 607-614. 

Eew studies have been done on the molecular features of gastrointestinal endocrine tumors. Allelic loss of llq has been detected in GI endocrine tumors associated with MENl, and LOH of 1 Iq is also present in a subset of sporadic GI endocrine tumors. Mutations of the MENl gene are present in approximately 30% of sporadic gastrinomas and in occasional midgut and hindgut endocrine tumors. In contrast to pancreatic endocrine tumors, the CpG island methylator phenotype is frequent in GI endocrine tumors. Beta-catenin exon 3 mutations are relatively common (38%) in these tumors, and up to 80% of the tumors show nuclear and cytoplasmic localization of the corresponding protein. Other studies, however, reported absence of exon 3 mutations, but nuclear f5-catenin was found in 30% of cases. In contrast, extra-GI endocrine tumors were negative for nuclear f5-catenin. 

Cytokeratin immunoreactivity is present in normal pancreatic endocrine cells and in approximately 90% of pancreatic endocrine tumors (PETs), whereas CK20... 

FIGURE 10.38 Distribution of markers in pancreatic endocrine tumors. SYN, synaptophysin NSE, neuron-specific enolase LMWCK, low-molecular-weight cytokeratin CgA, chromogranin A PC2, pro-convertase 2 PCM, peptidylglycine alpha-amidating enzyme PC3, proconvertase 3 NFP, neurofilament protein HCC(a), human chorionic gonadotropin alpha VIM, vimentin. 

FIGURE 10.40 Nonfunctional pancreatic endocrine tumor. Im-munoperoxidase stain for pancreatic polypeptide shows positivity in scattered individual tumor cells. 

FIGURE 10.41 Nonfunctional pancreatic endocrine tumor. Immu-noperoxidase stain for the alpha chain of human chorionic gonadotropin shows a few positive cells. 

VIP-producing tumors have been associated with the syndrome of WDHA. In a series of 28 cases of WDHA studied by Solcia and colleagues, VIP was present in 87% and peptide histidine methionine was present in 57% of cases.Growth hormone-releasing hormone and PP were present in 50% and 53% of cases, respectively. In addition to pancreatic endocrine tumors, ganglioneuromas and ganglioneuroblastomas have been associated with the syndrome of WDHA. 

Rare examples of serotonin-producing endocrine tumors may occur within the pancreas. Other tumors occurring as primary pancreatic endocrine tumors may produce growth hormone-releasing hormone (acromegaly), ACTH (Cushing s syndrome), and PTH or PTH-like peptide (hypercalcemia). Nonfunctional pancreatic endocrine tumors may contain scattered cells positive for a variety of hormones, most commonly PP and glucagon (Fig. 10.40). 

The alpha chain of hCG has been regarded as a marker of malignancy in pancreatic endocrine tumors and occurs in approximately 70% of cases (Fig. 10.41). More recent studies, however, have also... 

Bordi C, Pilato FP, D Adda T. Comparative study of sevetal NE matkers in pancreatic endocrine tumors. Virchows Arch A Pathol Anat Histopathol. 1988 413 387-398. 

Stivastava A, Hotnick JL. Immunohistochemical staining for CDX2, PDX-1, NESP-55 and TTF-7 can help distinguish gastrointestinal carcinoid tumors from pancreatic endocrine and pulmonary carcinoid tumors. Am J Surg Pathol. 2008 (E.pub). 

LaRosa S, Sessa E, Capella C, et al. Prognostic criteria in nonfunctioning pancreatic endocrine mmors. Virchows Arch. 85. 1996 429 323-333. 

Kimura N, Pilichowska M, Okamoto H, et al. Immunohistochemical expression of chromogranins A and B, prohormone convertases 2 and 3, and amidating enzyme in carcinoid tumors and pancreatic endocrine tumors. Mod Pathol. 2000 13 140-146. 

Heitz PU, Kasper M, Polak JM, Kloppel G. Pancreatic endocrine tumors Immunocytochemical analysis of 125 tumors. Hum Pathol. 1982 13 263-271. 

Heitz PU, Kasper M, Kloppel G, et al. Glycoprotein-hormone alpha-chain production by pancreatic endocrine tumors A specific marker for malignancy Immunocytochemical analysis of tumors of 155 patients. Cancer. 1983 51 277-282. 

Viale G, Doglioni G, Gambacorta M, et al. Progesterone receptor immunoreactivity in pancreatic endocrine tumors An immunocytochemical study of 156 NE tumors of the pancreas, gastrointestinal and respiratory tracts and skin. Cancer. 1992 70 2268-2277. 

Heitz PU, Komminoth P, Perren A, et al. Pancreatic endocrine tumours An introduction. In DeLellis RA, Lloyd RV, Heitz PU, Eng G, eds. Pathology and Genetics of Tumours of Endocrine Organs. WHO Classification of Tumours. Lyon, France lARG Press 2004 177-182. 

Deshpande V, Fernandez-del Gastillo G, Muzikansky A, et al. Gytokeratin 19 is a powerful predictor of survival in pancreatic endocrine tumors. Am J Surg Pathol. 2004 28 1145-1153. 

Goto A, Niki T, Terrado Y, et al. Prevalence of GD99 expression in pancreatic endocrine tumors (PETs). Histopathology. 2004 45 384-392. 

LaRosa S, Rigoli E, Uccella S, et al. Prognostic and biological significance of cytokeratin 19 in pancreatic endocrine tumors. Histopathology. 2007 50 597-606. 

Gouvelard A, Hu J, Steers G, et al. Identification of potential therapeutic targets by gene expression profiling in pancreatic endocrine tumors. Gastroenterology. 2006 131 1597-1610. 

Perren A, Anlauf M, Komminoth P. Molecular profiles of pancreatic endocrine tumors. Virchows Arch. 2007 451(Supp 1) S39-S46. 

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