title: Genetic alterations in poorly differentiated endocrine carcinomas of the gastrointestinal tract.
abstract: BACKGROUND
  The molecular pathogenesis of poorly differentiated endocrine carcinomas of the gastrointestinal tract (GI PDECs) remains unclear. It has been suggested that these lesions either originate from multipotent stem cells that also can serve as the origin of nonendocrine adenocarcinomas or arise due to the dedifferentiation of well-differentiated endocrine carcinomas (WDECs).
  
  
  METHODS
  Ten gastric and 9 colorectal PDECs, 9 gastric WDECs, and 12 colorectal carcinomas (CRCs) were analyzed for loss of heterozygosity (LOH) at 11q13 (MEN1), 17p13.1 (p53), 3p14.2 (FHIT), 3p21.3 (RASSF1A), and 18q23 (DCC/DPC4/Smad2), and for immunohistochemical expression of p53, FHIT, Rb, and p16.
  
  
  RESULTS
  PDECs exhibited high fractional allelic loss (FAL; 0.49), with frequent (> 40%) alterations in p53, Rb, MEN1, FHIT, and 18q. No significant differences were found between gastric and colorectal PDECs. Gastric WDECs also exhibited high FAL (0.44), with frequent alterations in Rb and/or p16, MEN1, and 3p21. CRCs exhibited a low level of FAL (0.23), with frequent (> 50%) p16 and p53 alterations. When gastric PDECs and WDECs were compared, substantial similarities were found with respect to FAL (0.42 vs. 0.44) and with respect to individual gene alterations, except in p53, which was consistently altered only in PDECs. CRCs, which were characterized by a lower FAL (0.56 vs. 0.23) and which lacked alterations in both 3p and Rb, were found to be significantly different from colorectal PDECs.
  
  
  CONCLUSIONS
  GI PDECs demonstrated a high level of chromosomal instability; consistent inactivation of both the p53 and p16/Rb pathways; and frequent LOH at 3p (possibly involving FHIT), the MEN1 locus, and 18q. The profile of genetic alterations in PDECs was more consistent with the profile in WDECs than with the profile in CRCs.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Parma, Parma, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Pizzi
authors.forename: Cinzia
authors.initials: C
authors.lastname: Azzoni
authors.forename: Daniela
authors.initials: D
authors.lastname: Bassi
authors.forename: Lorena
authors.initials: L
authors.lastname: Bottarelli
authors.forename: Massimo
authors.initials: M
authors.lastname: Milione
authors.forename: Cesare
authors.initials: C
authors.lastname: Bordi
mesh_terms: D017766:Acid Anhydride Hydrolases; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D004701:Endocrine Gland Neoplasms / Q000235:genetics*; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics; D016160:Retinoblastoma Protein / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D000099170:Bis(5'-adenosyl)triphosphatase