Succinate Dehydrogenase (SDHB): A New Marker of Malignancy in Midgut Carcinoids?

Introduction: The immunoistochemical (IHC) loss of SDHB expression was reported as a surrogate marker of malignancy in sporadic and familial pheocromocytomas/paragangliomas. SDHB loss is supposed to be tumorigenic (activation hypoxia signals). Aim(s): SDHB levels evaluation in advanced midgut carcinoids and its potential role as a prognostic marker. Materials and methods: Thirty-one midgut carcinoids were identified: 78% males, 22% females, median age 55.5 yrs (range 19-75). All pts were NET G1, stage IV synchronous liver metastases. 25/31 underwent surgical primary resection. 70% were up front treated with somatostatin analogues. SDHB and MIB1 expression were carried out in 19 primary tumors (T) and in 19 liver metastasis (M). In eleven pts, SDHB and MIB1 were tested both in T and in M. SDHB was evaluated with a semiquantitative scale considering staining intensity score 1 (low), 2 (high). Results: SDHB (2+), with a clear cytoplasmatic mitochondrial reactivity, was found in 77% (14/19) T, whilst loss of SDHB expression (1+) was detected in 90% (17/19) M. In eleven pts, the combined analysis (T+M), confirmed a loss of SDHB expression in 82% (9/11) M, compared to 18% (2/11) T. These data are inversely proportional to Mib-1% value that, on the contrary, increased in metastatic lesions: median (T) MIB1:0.7% v. median (M) MIB1: 1.54%. Conclusion: Our findings support a correlation between a loss of SDHB expression, increase of MIB1 and malignancy in advanced midgut carcinoids. A prospective evaluation is mandatory to clarify a possible correlation wth survival. [ABSTRACT FROM AUTHOR]