[600] Loss of Cables Expression in Neuroendocrine Tumors (NETs) of the Gastrointestinal Tract, Pancreas, and Lung

Thomas Arnason, Maria S Pino, Daniel C Chung, Heidi L Sapp, Daniel Rayson, Vikram Deshpande, Lawrence R Zukerberg. Massachusetts General Hospital, Boston, MA; Queen Elizabeth II HSC, Halifax, NS, Canada

Background: In the pathogenesis of NETs, several chromosomal deletions have been identified, but few tumor suppressor genes, apart from MEN1, have been implicated. Chromosome 18 deletions are present in nearly 70% of ileal NETs. The Cables gene, which maps to chromosome 18q11-12, is a tumor suppressor gene in human cancers. Loss of Cables expression has been detected in many carcinomas, including colon cancer, which has frequent chromosome 18 loss. There are no prior studies of Cables expression in NETs.
Design: IHC for Cables was applied to tissue microarrays containing FFPE tumor tissue from 310 NETs. Nuclear expression of Cables was interpreted as intact, partially lost, or completely lost and correlated with stage, grade, and survival in a subset.
Results: Cables expression was completely lost in 44% of 310 NETs tested. Cables expression was intact less often in ileal tumors (8%) compared to tumors from all other sites combined (35%, p<0.025) and compared to other small intestinal (SI) sites (51%, p<0.01).

Table 1
Primary siteComplete loss of CablesPartial loss of CablesCables intact
SI18(25%)17(24%)36(51)%
Ileum11(44%)12(48%)2(8%)
Pancreas31(43%)20(27%)22(30%)
Appendix4(40%)06(60%)
Lung74(57%)21(16%)36(27%)


Loss of Cables expression was not associated with a significant difference in stage or grade in a subset of primary pancreatic (n=34) and SI (n=32) NETs.

Table 2
ENETS* stageComplete loss of CablesPartial loss of CablesCables intact
14(18%)2(15%)5(16%)
2a2(9%)2(15%)6(19%)
2b3(14%)1(8%)6(19%)
3a3(14%)1(8%)0
3b6(27%)6(46%)10(32%)
44(18%)1(8%)4(13%)
Grade   
117(77%)12(92%)26(84%)
24(18%)1(8%)3(10%)
31(4%)02(6%)
*European NET Society

Complete loss of Cables expression was not associated with a difference in disease free or overall survival in a subset of 53 patients with pancreatic and SI NETs.


Conclusions: Cables expression is lost in a significant proportion of NETs. Ileal NETs have frequent deletions of chromosome 18, which is one mechanism for loss of Cables. Loss of Cables expression in NETs from other sites with infrequent chromosome 18 deletions suggests that Cables is lost by other mechanisms such as epigenetic silencing and suggests that Cables is a tumor suppressor gene in NETs.
Category: Gastrointestinal

Tuesday, March 5, 2013 1:00 PM

Poster Session IV # 115, Tuesday Afternoon

 

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