title: Malignancy-associated allelic losses on the X-chromosome in foregut but not in midgut endocrine tumours.
abstract: Information on genetic changes involved in the progression of gastroenteropancreatic (GEP) endocrine tumours is scanty. On the other hand, the identification of molecular markers of malignancy could be crucial for the prognostic evaluation of these neoplasms, which is hardly predictable on the basis of conventional histological criteria. An association of X-chromosome deletions with malignancy has already been found in gastric endocrine tumours. To investigate this further, a comparative loss of heterozygosity (LOH) analysis was performed on 17 pancreatic endocrine tumours (PETs) and 17 intestinal (ten ileal, six appendiceal, and one rectal) carcinoids from female patients. The relationship of X-chromosome LOH with the ploidy status of the neoplasms was also investigated. LOH was found in six of eight malignant PETs (60% of the informative markers), but was infrequent in the nine benign ones (4.5%). In contrast, although retention of heterozygosity was consistently observed in benign midgut tumours, LOH was infrequent in malignant carcinoids (15%). No correlation was found between LOH and the ploidy status. These results indicate an association between X-chromosome LOH and malignancy in foregut endocrine tumours. The lack of such an association in midgut carcinoids suggests that different molecular mechanisms are involved in the progression of these two categories of endocrine neoplasms, which are otherwise considered to be closely related. These findings emphasize the need for further molecular studies on GEP endocrine tumours, carefully subdivided according to their anatomical site of origin.
authors.affiliation: Department of Pathology and Laboratory Medicine, Section of Pathological Anatomy, University of Parma, Parma, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Pizzi
authors.forename: Tiziana
authors.initials: T
authors.lastname: D'Adda
authors.forename: Cinzia
authors.initials: C
authors.lastname: Azzoni
authors.forename: Guido
authors.initials: G
authors.lastname: Rindi
authors.forename: Piergiovanni
authors.initials: P
authors.lastname: Grigolato
authors.forename: Claudio
authors.initials: C
authors.lastname: Pasquali
authors.forename: Vito D
authors.initials: VD
authors.lastname: Corleto
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Delle Fave
authors.forename: Cesare
authors.initials: C
authors.lastname: Bordi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002276:Carcinoid Tumor / Q000235:genetics / Q000473:pathology; D002648:Child; D005260:Female; D006801:Humans; D007414:Intestinal Neoplasms / Q000235:genetics* / Q000473:pathology; D019656:Loss of Heterozygosity; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000235:genetics* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D011003:Ploidies; D016133:Polymerase Chain Reaction / Q000379:methods; D014960:X Chromosome / Q000235:genetics*