SDHB: A Marker of Malignancy in Familial and Sporadic Pheochromocytomas/Sympathethic Paragangliomas.
Annika Blank, Anja M Schmitt, Esther Korpershoek, Francien H van Nederveen, Thomas Rudolph, Nicole Weber, Raeto Strebel, Ronald de Krijger, Paul Komminoth, Aurel Perren. Klinikum Rechts der Isar, Technische Universitaet Muenchen, Munich, Germany; Josephine Nefkens Institute, Erasmus MC, University Medical Center, Rotterdam, Netherlands; University Hospital Zurich, Switzerland; University of Bern, Switzerland; City Hospital Triemli, Zurich, Switzerland
Background: To date there is no reliable histopathological marker of malignancy for pheochromocytomas/sympathetic paragangliomas (PCC/PGL). It is well known that PCC/PGL in the hereditary context of an SDHB germline mutation very often metastasize. The immunohistochemical loss of SDHB expression was recently shown to be a surrogate marker for the presence of an SDH germline mutation in PCC/PGL. SDHB loss is supposed to be tumorigenic via activation of hypoxia signals. Our aim was to clarify: 1. the potential use of SDHB immunohistochemistry as a marker of malignancy in PCC/PGL; and, 2. its association with classic hypoxia signalling.
Design: The protein expression of SDHB, Hif-1α and its targets CA-9 and GLUT-1 was examined by immunohistochemistry using a tissue micro array containing a series of familial and sporadic tumors of 115 patients. The obtained results were correlated with survival data which were available for 66 patients.
Results: In the tumor tissue of 12 of 99 patients a loss of SDHB protein expression was observed. In 5 of these 12 patients an SDHB germline mutation was present while in 4 patients no germline mutation was detected. In 3 patients mutational status remained unknown in parts. There was no association between loss of SDHB expression and increased classic hypoxia signalling as detected by HIF-1α, CA-9 or GLUT-1 immunohistochemistry. Loss of SDHB expression correlated significantly with a shortened disease specific survival.
Conclusions: Our findings do not support the current hypoxia hypothesis in malignant PCC/PGL. We propose SDHB protein loss as a marker of malignancy both in sporadic and in familial PCC/PGL.
Monday, February 28, 2011 8:45 AM
Platform Session: Section H 1, Monday Morning