P1.24 Loss of Succinate Dehydrogenase in Midgut Carcinoids as Prognostic Factor: A New Marker of Personalized Cancer Medicine in Neuroendocrine Tumours?

Abstract

ABSTRACT Background Gene mutations of the succinate dehydrogenase (SDH) complex have recently been involved in the pathogenesis of cancer cells. These mutations often are associated with SDH subunity B loss of activity and overexpression of HIF-1a, which play a central role in angiogenesis and cell proliferation. The immunoistochemical (IHC) loss of SDHB expression has recently been reported to be a surrogate marker of malignancy in sporadic and familial pheocromocytomas and paragangliomas via activation of hypoxia signals. Aims To evaluate SDHB levels expression in advanced midgut carcinoids and investigate its potential role as prognostic marker. Materials and methods 31 advanced midgut carcinoids were treated in our Istitution, including 24 males and 7 females, aged 55.5 yrs on average (range 19-75). All patients were G1 tumors with stage IV for synchronous liver metastases. 25/31 patients underwent surgical primary resection. IHC evaluation of the SDHB and MIB1 expression were carried out in 19 primary tumors (T) and 19 liver metastases (M). In 11 patients SDHB and MIB1 were tested in both T and M. SDHB was assessed according to the staining intensity scored 1 (low) or 2 (high) on the basis of the internal control represented by normal intestinal cells. Results High (2+) positivity for SDHB, with clear cytoplasmatic mitochondrial reactivity, was found in 14/19 (77%) T, whilst loss of SDHB expression (1+) was detected in 17/19 (90%) M. The combined analysis (T + M) confirmed the loss of SDHB expression in 9/11 (82%) metastases compared to 2/11 (18%) primary tumors. These findings were inversely proportional to Mib-1 distribution that was 1,54% in metastastic sites and 0.7% in the primaries, respectively. Conclusions This preliminary analysis suggests a possible correlation between SDHB expression loss (score 1+), MIB1 increase and biological aggressiveness of advanced midgut carcinoids. A more extensive clinico-biological evaluation is warranted to clarify its relationship with survival and explore the role of SDHB as predictive marker to response of antiangiogenetic agents. Download : Download full-size image Fig. 1 . SDHB immunoreactivity. a. SDHB staining in primitive ileal NET; b. SDHB staining in liver metastasis of ileal NET; c. SDHB staining in lymph node metastasis of ileal NET.