Succinate Dehydrogenase B Subunit Immunohistochemical Expression Predicts Aggressiveness in Well Differentiated Neuroendocrine Tumors of the Ileum

Immunohistochemical loss of the succinate dehydrogenase subunit B (SDHB) has recently been reported as a surrogate biomarker of malignancy in sporadic and familial pheocromocytomas and paragangliomas through the activation of hypoxia pathways. However, data on the prevalence and the clinical implica...

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Main Authors: Filippo G. de Braud, Giuseppe Pelosi, Vincenzo Mazzaferro, Patrick Maisonneuve, Flavia Melotti, Patrizia Gasparini, Massimo Milione, Sara Pusceddu
Format: Article
Language:English
Published: MDPI AG 2012-08-01
Series:Cancers
Subjects:
Online Access:http://www.mdpi.com/2072-6694/4/3/808
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author Filippo G. de Braud
Giuseppe Pelosi
Vincenzo Mazzaferro
Patrick Maisonneuve
Flavia Melotti
Patrizia Gasparini
Massimo Milione
Sara Pusceddu
author_facet Filippo G. de Braud
Giuseppe Pelosi
Vincenzo Mazzaferro
Patrick Maisonneuve
Flavia Melotti
Patrizia Gasparini
Massimo Milione
Sara Pusceddu
author_sort Filippo G. de Braud
collection DOAJ
description Immunohistochemical loss of the succinate dehydrogenase subunit B (SDHB) has recently been reported as a surrogate biomarker of malignancy in sporadic and familial pheocromocytomas and paragangliomas through the activation of hypoxia pathways. However, data on the prevalence and the clinical implications of SDHB immunoreactivity in ileal neuroendocrine tumors are still lacking. Thirty-one consecutive, advanced primary midgut neuroendocrine tumors and related lymph node or liver metastases from 24 males and seven females were immunohistochemically assessed for SDHB. All patients were G1 tumors (Ki-67 labeling index ≤2%). SDHB immunohistochemistry results were expressed as immunostaining intensity and scored as low or strong according to the internal control represented by normal intestinal cells. Strong positivity for SDHB, with granular cytoplasmatic reactivity, was found in 77% of primary tumors (T), whilst low SDHB expression was detected in 90% of metastases (M). The combined analysis (T+M) confirmed the loss of SDHB expression in 82% of metastases compared to 18% of primary tumors. SDHB expression was inversely correlated with Ki-67 labeling index, which accounted for 1.54% in metastastic sites and 0.7% in primary tumors. A correlation between SDHB expression loss, increased Ki-67 labeling index and biological aggressiveness was shown in advanced midgut neuroendocrine tumors, suggesting a role of tumor suppressor gene.
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spelling doaj.art-42aeef377e824432bdf47e3146c018172023-09-02T13:52:53ZengMDPI AGCancers2072-66942012-08-014380882010.3390/cancers4030808Succinate Dehydrogenase B Subunit Immunohistochemical Expression Predicts Aggressiveness in Well Differentiated Neuroendocrine Tumors of the IleumFilippo G. de BraudGiuseppe PelosiVincenzo MazzaferroPatrick MaisonneuveFlavia MelottiPatrizia GaspariniMassimo MilioneSara PuscedduImmunohistochemical loss of the succinate dehydrogenase subunit B (SDHB) has recently been reported as a surrogate biomarker of malignancy in sporadic and familial pheocromocytomas and paragangliomas through the activation of hypoxia pathways. However, data on the prevalence and the clinical implications of SDHB immunoreactivity in ileal neuroendocrine tumors are still lacking. Thirty-one consecutive, advanced primary midgut neuroendocrine tumors and related lymph node or liver metastases from 24 males and seven females were immunohistochemically assessed for SDHB. All patients were G1 tumors (Ki-67 labeling index ≤2%). SDHB immunohistochemistry results were expressed as immunostaining intensity and scored as low or strong according to the internal control represented by normal intestinal cells. Strong positivity for SDHB, with granular cytoplasmatic reactivity, was found in 77% of primary tumors (T), whilst low SDHB expression was detected in 90% of metastases (M). The combined analysis (T+M) confirmed the loss of SDHB expression in 82% of metastases compared to 18% of primary tumors. SDHB expression was inversely correlated with Ki-67 labeling index, which accounted for 1.54% in metastastic sites and 0.7% in primary tumors. A correlation between SDHB expression loss, increased Ki-67 labeling index and biological aggressiveness was shown in advanced midgut neuroendocrine tumors, suggesting a role of tumor suppressor gene.http://www.mdpi.com/2072-6694/4/3/808midgutneuroendocrine tumorsSDHBimmunohistochemistryKi-67 antigen
spellingShingle Filippo G. de Braud
Giuseppe Pelosi
Vincenzo Mazzaferro
Patrick Maisonneuve
Flavia Melotti
Patrizia Gasparini
Massimo Milione
Sara Pusceddu
Succinate Dehydrogenase B Subunit Immunohistochemical Expression Predicts Aggressiveness in Well Differentiated Neuroendocrine Tumors of the Ileum
Cancers
midgut
neuroendocrine tumors
SDHB
immunohistochemistry
Ki-67 antigen
title Succinate Dehydrogenase B Subunit Immunohistochemical Expression Predicts Aggressiveness in Well Differentiated Neuroendocrine Tumors of the Ileum
title_full Succinate Dehydrogenase B Subunit Immunohistochemical Expression Predicts Aggressiveness in Well Differentiated Neuroendocrine Tumors of the Ileum
title_fullStr Succinate Dehydrogenase B Subunit Immunohistochemical Expression Predicts Aggressiveness in Well Differentiated Neuroendocrine Tumors of the Ileum
title_full_unstemmed Succinate Dehydrogenase B Subunit Immunohistochemical Expression Predicts Aggressiveness in Well Differentiated Neuroendocrine Tumors of the Ileum
title_short Succinate Dehydrogenase B Subunit Immunohistochemical Expression Predicts Aggressiveness in Well Differentiated Neuroendocrine Tumors of the Ileum
title_sort succinate dehydrogenase b subunit immunohistochemical expression predicts aggressiveness in well differentiated neuroendocrine tumors of the ileum
topic midgut
neuroendocrine tumors
SDHB
immunohistochemistry
Ki-67 antigen
url http://www.mdpi.com/2072-6694/4/3/808
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