Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2012) 28 OC5.5

SFEBES2012 Oral Communications Growth, tumours and pituitary (8 abstracts)

Role of the hypoxic signalling pathways in the histopathological prediction of malignancy in phaeochromocytomas and paragangliomas

David Pinato 1, , Radha Ramachandran 1 , Samin Toloue Kalami Toussi 1 , Marco Vergine 2 , Nyethane Ngo 2 , Rohini Sharma 1 , Bernard Khoo 5 , Karim Meeran 1 , Fausto Palazzo 3 , Niamh Martin 1 , Roberto Dina 2 & Tricia Tan 1

1Imperial College Center for Endocrinology, Imperial College, London, United Kingdom; 2Department of Histopathology, Imperial College, London, United Kingdom; 3Department of Surgery, Imperial College, London, United Kingdom; 4Clinical and Experimental Medicine, Università del Piemonte Orientale "A. Avogadro", Novara, Italy; 5Department of Endocrinology, University College London, London, United Kingdom.

Backgeound and Aims: Phaeochromocytomas (PCC) and paragangliomas (PGL) are mostly benign sympathoadrenal tumours. However, there are no available markers to predict a malignant course. Since hypoxia is involved in the pathogenesis of these tumours, we aimed to qualify the relevance of the mammalian Target of Rapamycin (m-TOR) and hypoxic pathways in benign and malignant PCC/PGL.

Methods: Tissue microarray (TMA) blocks were constructed with 80 PCC/PGL, including 12 malignant cases and 1 recurrence, and 20 normal adrenomedullary samples. TMA sections were immunostained for Hypoxia inducible factor 1α (Hif-1α), Vascular Endothelial Growth Factor A (VEGF-A), m-TOR and Carbonic Anhydrase IX (CaIX).

Results: Seventy-nine consecutive PCC (63%) and PGL (30%) were included, 5 (6%) had bilateral adrenal disease. Median tumour size was 5.0 cm (range 0.8–14). Capsular (CI) and vascular invasion (VI) were present in 9 (11%) and 6 (8%) of the specimens. Fourteen cases displayed tumour necrosis (17%). Genotype was available in 22 syndromic cases: SDH-B (14%), SDH-D (4%), RET (60%), NF-1 (8%), VHL (14%). m-TOR and CaIX expression was upregulated in PCC/PGL compared to controls but no difference was found for VEGF-A and Hif-1α. VEGF-A, Hif-1α, CaIX and m-TOR expression did not predict malignant behaviour, overall and disease free survival. VI was the only significant predictor of malignancy (P<0.01). A trend with malignant phenotype was seen for VEGF-A (P=0.06), whilst CaIX expression correlated with CI and extra-adrenal disease (P<0.01). CaIX expression was positively associated with VHL mutation (P<0.01).

Conclusion: CaIX and m-TOR are upregulated in PCC/PGL and hence may play a significant role in the pathogenesis these tumours. VI was the only predictor of malignancy in our study. CaIX immunohistochemical analysis may improve the cost effectiveness of genetic screening for VHL in patients presenting with PCC. A larger study is needed to confirm the clinical value of these preliminary conclusions.

Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Funding: No specific grant from any funding agency in the public, commercial or not-for-profit sector.


Article tools

My recent searches

No recent searches.