Pancreatic tumors 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. 

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. 

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. 

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. 

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. 

Cai YC, Banner B, Glickman J, Odze RD. Cytokeratin 7 and 20 and thyroid transcription factor-1 can help distinguish pulmonary from gastrointestinal carcinoid and pancreatic endocrine tumors. Hum Pathol. 2001 32 1087-1093. 

Srivastava A, Padilla O, Fischer-Golbrie R, et al. Neuroendocrine secretory protein-55 (NESP-55) expression discriminates pancreatic endocrine tumors and pheochromocytomas from gastrointestinal and pulmonary carcinoids. Am J Surg Pathol. 2004 28 1371-1378. 

Heitz PU, Komminoth P, Perren A. Pancreatic endocrine tumors Introduction. In Delellis RA, Lloyd RV, Heitz PU, Eng C, eds. WHO Classification of Tumors. Pathology and Genetics of Tumours od Endocrine Organs. Lyon, France lARC Press 2004 177-182. 

Chetty R, Asa SL. Pancreatic endocrine tumors an update. Adv Anat Pathol. 2004-,11 202-210. 

Mukai K, Grotting JC, Greider MH, Rosai J. Retrospective study of 77 pancreatic endocrine tumors using the immunoper-oxidase method. Am Surg Pathol. 1982 6 387-399. 

Dayal Y, Lin HD, Tallberg K, et al. Immunocytochemical demonstration of growth hormone-releasing factor in gastrointestinal and pancreatic endocrine tumors. Am J Clin Pathol. 1986 85 13-20. 

Papotti M, Bongiovanni M, Volante M, et al. Expression of somatostatin receptor types 1-5 in 81 cases of gastrointestinal and pancreatic endocrine tumors. A correlative immunohistochemical and reverse-transcriptase polymerase chain reaction analysis. Virchows Arch. 2002 440 461-475. 

Stumpf E, Aalto Y, Hoog A, et al. Chromosomal alterations in human pancreatic endocrine tumors. Genes Chromosomes Cancer. 2000 29 83-87. 

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