Loss of succinate dehydrogenase subunit B (SDHB) as a prognostic factor in advanced ileal well-differentiated neuroendocrine tumors

Massimo Milione, Patrick Maisonneuve, Alessio Pellegrinelli, Sara Pusceddu, Giovanni Centonze, Francesca Dominoni, Cecilia Brambilla, Manila Rubino, Antongiulio Faggiano, Roberto Buzzoni, Laura Concas, Luca Giacomelli, Jorgelina Coppa, Vincenzo Mazzaferro, Filippo de Braud

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Abstract

PURPOSE: Abnormal expression of succinate dehydrogenase, (SDH), in particular of the B subunit (SDHB), is implicated in the pathogenesis of neuroendocrine tumors. This study evaluates the distribution of SDHB in WHO grading G1 and G2 intestinal, well-differentiated neuroendocrine tumors and corresponding lymph node or liver metastases.

METHODS: We collected ileal well-differentiated neuroendocrine tumors specimens from consecutive patients with prior primary resection and distant synchronous or metachronous liver metastases. We obtained 195 specimens from primary tumors (n = 106) and metastases (n = 89). The expression (E) of SDHB and the immunostaining intensity (I) were evaluated semiquantitatively and combined into a single score. SDHB score was evaluated in primitive tumor and metastatic specimens.

RESULTS: SDHB was found in all tumor cells. Mean SDHB expression was 72.7 % ± 17.1 % in primitive specimens and 27.9 % ± 24.6 % in metastatic specimens (p < 0.0001). SDH intensity was higher in primitive specimens (p < 0.0001). SDHB score was 9-12 in 96 specimens of the primitive group and 2 metastatic specimens (p < 0.0001). None of the analyzed parameters was predictive of overall survival in the primitive subset. In the metastatic subset, loss of SDHB expression, intensity, and score were prognostic factors for survival. Lower expression and intensity of SDHB in metastatic lesions were associated with longer overall survival. When combining SDHB score and Ki-67 % in the metastatic subset, a lower SDHB score was associated with prolonged overall survival, independently from Ki-67 %.

CONCLUSIONS: SDHB score was different in primitive and metastatic specimens. The combination of SDHB score and Ki-67 % was a stronger predictor of overall survival than Ki-67 % alone. This stratification might help predict survival.

Original languageEnglish
JournalEndocrine
DOIs
Publication statusE-pub ahead of print - Nov 30 2016

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Succinate Dehydrogenase
Neuroendocrine Tumors
Survival
Neoplasm Metastasis
Neoplasms
Liver

Keywords

  • Journal Article

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Loss of succinate dehydrogenase subunit B (SDHB) as a prognostic factor in advanced ileal well-differentiated neuroendocrine tumors. / Milione, Massimo; Maisonneuve, Patrick; Pellegrinelli, Alessio; Pusceddu, Sara; Centonze, Giovanni; Dominoni, Francesca; Brambilla, Cecilia; Rubino, Manila; Faggiano, Antongiulio; Buzzoni, Roberto; Concas, Laura; Giacomelli, Luca; Coppa, Jorgelina; Mazzaferro, Vincenzo; de Braud, Filippo.

In: Endocrine, 30.11.2016.

Research output: Contribution to journalArticle

@article{45b223cef2f24d6db8439d962324cf46,
title = "Loss of succinate dehydrogenase subunit B (SDHB) as a prognostic factor in advanced ileal well-differentiated neuroendocrine tumors",
abstract = "PURPOSE: Abnormal expression of succinate dehydrogenase, (SDH), in particular of the B subunit (SDHB), is implicated in the pathogenesis of neuroendocrine tumors. This study evaluates the distribution of SDHB in WHO grading G1 and G2 intestinal, well-differentiated neuroendocrine tumors and corresponding lymph node or liver metastases.METHODS: We collected ileal well-differentiated neuroendocrine tumors specimens from consecutive patients with prior primary resection and distant synchronous or metachronous liver metastases. We obtained 195 specimens from primary tumors (n = 106) and metastases (n = 89). The expression (E) of SDHB and the immunostaining intensity (I) were evaluated semiquantitatively and combined into a single score. SDHB score was evaluated in primitive tumor and metastatic specimens.RESULTS: SDHB was found in all tumor cells. Mean SDHB expression was 72.7 {\%} ± 17.1 {\%} in primitive specimens and 27.9 {\%} ± 24.6 {\%} in metastatic specimens (p < 0.0001). SDH intensity was higher in primitive specimens (p < 0.0001). SDHB score was 9-12 in 96 specimens of the primitive group and 2 metastatic specimens (p < 0.0001). None of the analyzed parameters was predictive of overall survival in the primitive subset. In the metastatic subset, loss of SDHB expression, intensity, and score were prognostic factors for survival. Lower expression and intensity of SDHB in metastatic lesions were associated with longer overall survival. When combining SDHB score and Ki-67 {\%} in the metastatic subset, a lower SDHB score was associated with prolonged overall survival, independently from Ki-67 {\%}.CONCLUSIONS: SDHB score was different in primitive and metastatic specimens. The combination of SDHB score and Ki-67 {\%} was a stronger predictor of overall survival than Ki-67 {\%} alone. This stratification might help predict survival.",
keywords = "Journal Article",
author = "Massimo Milione and Patrick Maisonneuve and Alessio Pellegrinelli and Sara Pusceddu and Giovanni Centonze and Francesca Dominoni and Cecilia Brambilla and Manila Rubino and Antongiulio Faggiano and Roberto Buzzoni and Laura Concas and Luca Giacomelli and Jorgelina Coppa and Vincenzo Mazzaferro and {de Braud}, Filippo",
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doi = "10.1007/s12020-016-1180-6",
language = "English",
journal = "Endocrine",
issn = "1355-008X",
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TY - JOUR

T1 - Loss of succinate dehydrogenase subunit B (SDHB) as a prognostic factor in advanced ileal well-differentiated neuroendocrine tumors

AU - Milione, Massimo

AU - Maisonneuve, Patrick

AU - Pellegrinelli, Alessio

AU - Pusceddu, Sara

AU - Centonze, Giovanni

AU - Dominoni, Francesca

AU - Brambilla, Cecilia

AU - Rubino, Manila

AU - Faggiano, Antongiulio

AU - Buzzoni, Roberto

AU - Concas, Laura

AU - Giacomelli, Luca

AU - Coppa, Jorgelina

AU - Mazzaferro, Vincenzo

AU - de Braud, Filippo

PY - 2016/11/30

Y1 - 2016/11/30

N2 - PURPOSE: Abnormal expression of succinate dehydrogenase, (SDH), in particular of the B subunit (SDHB), is implicated in the pathogenesis of neuroendocrine tumors. This study evaluates the distribution of SDHB in WHO grading G1 and G2 intestinal, well-differentiated neuroendocrine tumors and corresponding lymph node or liver metastases.METHODS: We collected ileal well-differentiated neuroendocrine tumors specimens from consecutive patients with prior primary resection and distant synchronous or metachronous liver metastases. We obtained 195 specimens from primary tumors (n = 106) and metastases (n = 89). The expression (E) of SDHB and the immunostaining intensity (I) were evaluated semiquantitatively and combined into a single score. SDHB score was evaluated in primitive tumor and metastatic specimens.RESULTS: SDHB was found in all tumor cells. Mean SDHB expression was 72.7 % ± 17.1 % in primitive specimens and 27.9 % ± 24.6 % in metastatic specimens (p < 0.0001). SDH intensity was higher in primitive specimens (p < 0.0001). SDHB score was 9-12 in 96 specimens of the primitive group and 2 metastatic specimens (p < 0.0001). None of the analyzed parameters was predictive of overall survival in the primitive subset. In the metastatic subset, loss of SDHB expression, intensity, and score were prognostic factors for survival. Lower expression and intensity of SDHB in metastatic lesions were associated with longer overall survival. When combining SDHB score and Ki-67 % in the metastatic subset, a lower SDHB score was associated with prolonged overall survival, independently from Ki-67 %.CONCLUSIONS: SDHB score was different in primitive and metastatic specimens. The combination of SDHB score and Ki-67 % was a stronger predictor of overall survival than Ki-67 % alone. This stratification might help predict survival.

AB - PURPOSE: Abnormal expression of succinate dehydrogenase, (SDH), in particular of the B subunit (SDHB), is implicated in the pathogenesis of neuroendocrine tumors. This study evaluates the distribution of SDHB in WHO grading G1 and G2 intestinal, well-differentiated neuroendocrine tumors and corresponding lymph node or liver metastases.METHODS: We collected ileal well-differentiated neuroendocrine tumors specimens from consecutive patients with prior primary resection and distant synchronous or metachronous liver metastases. We obtained 195 specimens from primary tumors (n = 106) and metastases (n = 89). The expression (E) of SDHB and the immunostaining intensity (I) were evaluated semiquantitatively and combined into a single score. SDHB score was evaluated in primitive tumor and metastatic specimens.RESULTS: SDHB was found in all tumor cells. Mean SDHB expression was 72.7 % ± 17.1 % in primitive specimens and 27.9 % ± 24.6 % in metastatic specimens (p < 0.0001). SDH intensity was higher in primitive specimens (p < 0.0001). SDHB score was 9-12 in 96 specimens of the primitive group and 2 metastatic specimens (p < 0.0001). None of the analyzed parameters was predictive of overall survival in the primitive subset. In the metastatic subset, loss of SDHB expression, intensity, and score were prognostic factors for survival. Lower expression and intensity of SDHB in metastatic lesions were associated with longer overall survival. When combining SDHB score and Ki-67 % in the metastatic subset, a lower SDHB score was associated with prolonged overall survival, independently from Ki-67 %.CONCLUSIONS: SDHB score was different in primitive and metastatic specimens. The combination of SDHB score and Ki-67 % was a stronger predictor of overall survival than Ki-67 % alone. This stratification might help predict survival.

KW - Journal Article

U2 - 10.1007/s12020-016-1180-6

DO - 10.1007/s12020-016-1180-6

M3 - Article

JO - Endocrine

JF - Endocrine

SN - 1355-008X

ER -