PMID- 8604810
OWN - NLM
STAT- MEDLINE
DCOM- 19960514
LR  - 20190821
IS  - 0147-5185 (Print)
IS  - 0147-5185 (Linking)
VI  - 20
IP  - 4
DP  - 1996 Apr
TI  - Involvement of BCL-2 oncoprotein in the development of enterochromaffin-like cell 
      gastric carcinoids.
PG  - 433-41
AB  - To evaluate the involvement of the apoptosis-suppressing protein BCL-2 in the 
      gastrin-dependent mechanism of induction of gastric enterochromaffin-like (ECL) 
      cell carcinoids, the endocrine cell of the oxyntic mucosa were 
      immunohistochemically investigated in (a) 10 normogastrinemic subjects with 
      histologically normal gastric mucosa; (b) 22 patients with endocrine cell 
      hyperplasia and affected by hypergastrinemic conditions with different risk of 
      gastric carcinoid development, such as sporadic Zollinger-Ellison syndrome (sZES; 
      n = 9), ZES associated with multiple endocrine neoplasia-1 (MEN-1; n = 4), and 
      atrophic fundal gastritis (AFG; n = 9); (c) 14 patients with ECL gastric 
      carcinoids accounting for a total of 31 tumors investigated. In the normal 
      oxyntic mucosa, BCL-2 was consistently expressed by a subset of endocrine cells 
      accounting for 50.0% (median; range, 24.6-74.0%) of the total number of endocrine 
      cells immunostained for chromogranin A (CgA) in consecutive sections. BCL-2 
      immunoreactive cells were located mostly in the middle mucosal layer, suggesting 
      a role for the protein during downward migration of maturing endocrine cells. No 
      BCL-2 immunoreactivity was found in other specialized gastric epithelial cells. 
      Expression of BCL-2 by hyperplastic oxyntic endocrine cells (mostly ECL cells) 
      varied in parallel with the risk of carcinoid development. In fact, the ratio of 
      BCL-2- to CgA-immunoreactive cells was reduced (median, 4.6%; p less than 0.0001; 
      range, 0.9-42.0%) in sZES, a condition showing virtually no risk, unchanged 
      (median, 55.6%; range 29.4-83.8 %) in cases of MEN-1/ZES with intermediate risk, 
      and increased (median 87.6%; p less than 0.014; range, 48.8-199.4%) in cases of 
      AFG, a condition at the highest risk of carcinoid. In ECL cell carcinoids, BCL-2 
      expression varied markedly from one tumor to another even in the same patient and 
      was low or absent in most cases. In both hyperplastic and neoplastic ECL cells, 
      an inverse relation between BCL-2 expression and CgA immunoreactivity, that is, 
      the cell granule content, was found. These results suggest that BCL-2 expression 
      by hyperplastic ECL cells is independent of the influence of serum gastrin and 
      may contribute to the development of ECL cell carcinoid tumors by extending cell 
      exposure to oncogenic factors. Once a carcinoid tumor is established, BCL-2 
      expression becomes inconsistent.
FAU - Azzoni, C
AU  - Azzoni C
AD  - Institute of Anatomic Pathology, University of Parma, Italy.
FAU - Doglioni, C
AU  - Doglioni C
FAU - Viale, G
AU  - Viale G
FAU - Delle Fave, G
AU  - Delle Fave G
FAU - De Boni, M
AU  - De Boni M
FAU - Caruana, P
AU  - Caruana P
FAU - Ferraro, G
AU  - Ferraro G
FAU - Bordi, C
AU  - Bordi C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Surg Pathol
JT  - The American journal of surgical pathology
JID - 7707904
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Carcinoid Tumor/chemistry/genetics/*pathology
MH  - Enterochromaffin Cells/chemistry/*pathology
MH  - Female
MH  - Gastric Mucosa/chemistry/pathology
MH  - Genes, myc
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Protein-Tyrosine Kinases/genetics
MH  - Proto-Oncogene Proteins/*genetics
MH  - Proto-Oncogene Proteins c-bcl-2
MH  - Stomach Neoplasms/chemistry/genetics/*pathology
EDAT- 1996/04/01 00:00
MHDA- 1996/04/01 00:01
CRDT- 1996/04/01 00:00
PHST- 1996/04/01 00:00 [pubmed]
PHST- 1996/04/01 00:01 [medline]
PHST- 1996/04/01 00:00 [entrez]
AID - 10.1097/00000478-199604000-00006 [doi]
PST - ppublish
SO  - Am J Surg Pathol. 1996 Apr;20(4):433-41. doi: 10.1097/00000478-199604000-00006.