title: First report on metastasizing small bowel carcinoids in first-degree relatives in three generations.
abstract: OBJECTIVE
  There is an established association between the multiple endocrine neoplasia type 1 (MEN 1) syndrome and foregut carcinoids. Some registry studies also indicate that offspring to carcinoid patients run an increased risk of developing a carcinoid tumor themselves. However, there are only scattered reports of gastrointestinal carcinoids in two generations. The aim of this study was to describe the clinical characteristics as well as the histopathological, immunohistochemical (IHC) and genetic data of metastasizing ileal carcinoids in three consecutive first-degree relatives.
  
  
  METHODS
  The histopathological and IHC analyses were performed on newly cut sections of the tumor specimens and included growth pattern, proliferation index (Ki-67) as well as expression of established neuroendocrine markers and recently introduced cocaine-amphetamine-regulated transcript (CART). The genetic analyses were focused on establishing whether a connection with the MEN 1 syndrome existed in this family, by means of mutation screening using polymerase chain reaction, multiple ligation-dependent probe amplification, and genotyping using fluorescent-labeled microsatellite markers.
  
  
  RESULTS
  Histopathology and IHC revealed that the tumors were virtually identical, with only minor differences in proliferation index and expression of CART. Genetic analyses indicated that the inheritance of the small bowel carcinoids in the family was not linked to the MEN1 gene.
  
  
  CONCLUSIONS
  Metastasizing small bowel carcinoids have been found in first-degree relatives in three consecutive generations. All three tumors were very similar when characterized by histopathology and IHC. Based on clinical findings and genetic analyses, it seems unlikely, although not completely excluded, that inheritance was linked to the MEN 1 syndrome.
authors.affiliation: Department of Surgery, Ryhov Hospital, Jönköping, Sweden.
authors.forename: Johannes
authors.initials: J
authors.lastname: Järhult
authors.forename: Kalle
authors.initials: K
authors.lastname: Landerholm
authors.forename: Sture
authors.initials: S
authors.lastname: Falkmer
authors.forename: Magnus
authors.initials: M
authors.lastname: Nordenskjöld
authors.forename: Frank
authors.initials: F
authors.lastname: Sundler
authors.forename: Nils
authors.initials: N
authors.lastname: Wierup
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D002276:Carcinoid Tumor / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D007414:Intestinal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
chemical_list: D014408:Biomarkers, Tumor; C105373:MEN1 protein, human; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein