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 |
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Erscheinungsjahr: |
2017 |
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Erschienen: |
2017 |
Enthalten in: |
Zur Gesamtaufnahme - volume:161 |
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Enthalten in: |
Surgery - 161(2017), 3 vom: 03. März, Seite 753-759 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Roland, Christina L [VerfasserIn] |
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Links: |
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Themen: |
Journal Article |
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Anmerkungen: |
Date Completed 13.07.2017 Date Revised 13.11.2018 published: Print-Electronic Citation Status MEDLINE |
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doi: |
10.1016/j.surg.2016.09.002 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM265949963 |
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245 | 1 | 0 | |a Loss of DPC4/SMAD4 expression in primary gastrointestinal neuroendocrine tumors is associated with cancer-related death after resection |
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520 | |a Copyright © 2016 Elsevier Inc. All rights reserved. | ||
520 | |a 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 | ||
520 | |a 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 | ||
520 | |a 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) | ||
520 | |a 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 | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 4 | |a Research Support, N.I.H., Extramural | |
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700 | 1 | |a Chatterjee, Deyali |e verfasserin |4 aut | |
700 | 1 | |a Estrella, Jeannelyn |e verfasserin |4 aut | |
700 | 1 | |a Rashid, Asif |e verfasserin |4 aut | |
700 | 1 | |a Katz, Matthew H |e verfasserin |4 aut | |
700 | 1 | |a Aloia, Thomas A |e verfasserin |4 aut | |
700 | 1 | |a Lee, Jeffrey E |e verfasserin |4 aut | |
700 | 1 | |a Dasari, Arvind |e verfasserin |4 aut | |
700 | 1 | |a Yao, James C |e verfasserin |4 aut | |
700 | 1 | |a Fleming, Jason B |e verfasserin |4 aut | |
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