Loss of DPC4/SMAD4 expression in primary gastrointestinal neuroendocrine tumors is associated with cancer-related death after resection

Copyright © 2016 Elsevier Inc. All rights reserved..

BACKGROUND: Gastrointestinal neuroendocrine tumors have frequent loss of DPC4/SMAD4 expression, a known tumor suppressor. The impact of SMAD4 loss on gastrointestinal neuroendocrine tumors aggressiveness or cancer-related patient outcomes is not defined. We examined the expression of SMAD4 in resected gastrointestinal neuroendocrine tumors and its impact on oncologic outcomes.

METHODS: Patients who underwent complete curative operative resection of gastrointestinal neuroendocrine tumors were identified retrospectively (n = 38). Immunohistochemical staining for SMAD4 expression was scored by a blinded pathologist and correlated with clinicopathologic features and oncologic outcomes.

RESULTS: Twenty-nine percent of the gastrointestinal neuroendocrine tumors were SMAD4-negative and 71% SMAD4-positive. Median overall survival was 155 months (95% confidence interval, 102-208 months). Loss of SMAD4 was associated with both decreased median disease-free survival (28 months; 95% confidence interval, 16-40) months compared with 223 months (95% confidence interval, 3-443 months) for SMAD4-positive patients (P = .03) and decreased median disease-specific survival (SMAD4: 137 [95% confidence interval, 81-194] months versus SMAD4-positive: 204 [95% confidence interval, 143-264] months; P = .04). This translated into a decrease in median overall survival (SMAD4-negative: 125 (95% confidence interval, 51-214) months versus SMAD4-positive: 185 (95% confidence interval, 138-232) months; P = .02).

CONCLUSION: Consistent with the known biology of the DPC4/SMAD4 gene, an absence of its protein expression in primary gastrointestinal neuroendocrine tumors was negatively associated with outcomes after curative operative resection.

Medienart:

E-Artikel

Erscheinungsjahr:

2017

Erschienen:

2017

Enthalten in:

Zur Gesamtaufnahme - volume:161

Enthalten in:

Surgery - 161(2017), 3 vom: 03. März, Seite 753-759

Sprache:

Englisch

Beteiligte Personen:

Roland, Christina L [VerfasserIn]
Starker, Lee F [VerfasserIn]
Kang, Y [VerfasserIn]
Chatterjee, Deyali [VerfasserIn]
Estrella, Jeannelyn [VerfasserIn]
Rashid, Asif [VerfasserIn]
Katz, Matthew H [VerfasserIn]
Aloia, Thomas A [VerfasserIn]
Lee, Jeffrey E [VerfasserIn]
Dasari, Arvind [VerfasserIn]
Yao, James C [VerfasserIn]
Fleming, Jason B [VerfasserIn]

Links:

Volltext

Themen:

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
SMAD4 protein, human
Smad4 Protein

Anmerkungen:

Date Completed 13.07.2017

Date Revised 13.11.2018

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.surg.2016.09.002

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM265949963