Endocrine tumours of the gastrointestinal tract: aetiology, molecular pathogenesis and genetics.
Endocrine tumours of the gut and pancreas originate from cells of the diffuse endocrine system and are characterised by the production of a wide variety of bioactive substances including growth factors. Two major tumour categories are distinguished-well-differentiated and poorly differentiated neoplasms-with distinct phenotypes and significantly diverse clinical behaviour. Here, genetic background data are summarised on an anatomical basis for tumours of foregut, midgut and hindgut derivatives. For well-differentiated tumours, independent techniques identified the abnormality of multiple chromosomal sites and genes, pointing to a complex genetic background. Differences in foregut tumours compared with midgut and hindgut tumours are, however, outlined. The multiple endocrine neoplasia syndrome type 1 (MEN1) gene is reported to be involved in about one-third of sporadic foregut endocrine tumours and exceptionally in midgut and hindgut tumours. Similarly, X chromosome markers are associated with malignant behaviour in foregut tumours only. For poorly differentiated carcinomas, a high degree of chromosomal instability is the common genetic trait independent of tumour site and frequently involving the p53 gene.
Rindi
Guido
G
Department of Pathology and Laboratory Medicine, Section of Anatomic Pathology, University of Parma, Italy. guido.rindi@unipr.it
Bordi
Cesare
C
D018278:Carcinoma, Neuroendocrine / Q000235:genetics* / Q000473:pathology; D002454:Cell Differentiation; D005770:Gastrointestinal Neoplasms / Q000235:genetics* / Q000473:pathology; D016147:Genes, Tumor Suppressor / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D008745:Methylation; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology; D015291:Transforming Growth Factors / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000235:genetics
C105373:MEN1 protein, human; D011518:Proto-Oncogene Proteins; C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins; D015291:Transforming Growth Factors