First report on metastasizing small bowel carcinoids in first-degree relatives in three generations

Neuroendocrinology. 2010;91(4):318-23. doi: 10.1159/000299790. Epub 2010 May 12.

Abstract

Background/aims: 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.

Conclusion: 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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics
  • Carcinoid Tumor / genetics*
  • Carcinoid Tumor / metabolism
  • Carcinoid Tumor / pathology*
  • DNA Mutational Analysis
  • Female
  • Genetic Predisposition to Disease*
  • Humans
  • Immunohistochemistry
  • Intestinal Neoplasms / genetics*
  • Intestinal Neoplasms / metabolism
  • Intestinal Neoplasms / pathology
  • Male
  • Middle Aged
  • Mutation
  • Neoplasm Metastasis
  • Nerve Tissue Proteins / biosynthesis
  • Pedigree
  • Polymerase Chain Reaction
  • Proto-Oncogene Proteins / genetics

Substances

  • Biomarkers, Tumor
  • MEN1 protein, human
  • Nerve Tissue Proteins
  • Proto-Oncogene Proteins
  • cocaine- and amphetamine-regulated transcript protein