Massimo Milione1, Patrick Maisonneuve2, Alessio Pellegrinelli3, Sara Pusceddu4, Giovanni Centonze3, Francesca Dominoni3, Cecilia Brambilla3, Manila Rubino5, Antongiulio Faggiano5, Roberto Buzzoni4, Laura Concas4, Luca Giacomelli6, Jorgelina Coppa7, Vincenzo Mazzaferro7, Filippo de Braud4. 1. 1st Division of Pathology, Department of Pathology and Laboratory Medicine, IRCCS, Milan, Italy. Massimo.milione@istitutotumori.mi.it. 2. Division of Epidemiology and Biostatistics, European Institute of oncology (IEO), Milan, Italy. 3. 1st Division of Pathology, Department of Pathology and Laboratory Medicine, IRCCS, Milan, Italy. 4. Departement of Medical Oncology, IRCCS Foundation National Cancer Institute, Milan, Italy. 5. Istituto Nazionale per lo studio e la cura dei tumori "Fondazione G. Pascale"-IRCCS, Naples, Italy. 6. University of Genoa, Genoa, Italy. 7. Department of Surgery, G.I. Surgery and Liver Transplantation, Istituto Nazionale Tumori (National Cancer Institute), Milan, Italy.
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.
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.
Authors: G Capurso; S Lattimore; T Crnogorac-Jurcevic; F Panzuto; M Milione; V Bhakta; N Campanini; S M Swift; C Bordi; G Delle Fave; N R Lemoine Journal: Endocr Relat Cancer Date: 2006-06 Impact factor: 5.678
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Authors: James C Yao; Manal Hassan; Alexandria Phan; Cecile Dagohoy; Colleen Leary; Jeannette E Mares; Eddie K Abdalla; Jason B Fleming; Jean-Nicolas Vauthey; Asif Rashid; Douglas B Evans Journal: J Clin Oncol Date: 2008-06-20 Impact factor: 44.544