Endocrine Abstracts

Objectives: Adrenocortical carcinoma (ACC) is a rare tumor with poor prognosis and limited therapeutic options. Survivin is an anti-apoptotic molecule expressed by neoplastic and tumor-specific endothelial cells of various carcinomas, but rarely or only weakly in normal differentiated tissue. In melanoma and pancreatic cancer, preliminary results of a survivin vaccination trial (www.clinicaltrials.gov) indicated that an immunological response in patients is often paralleled by tumor control. Hence, we investigated, whether survivin may also be a reasonable target for an immunotherapy in ACC.

Methods: We performed survivin real-time-PCR in 14 ACCs and 13 normal adrenals. In addition, survivin protein was analysed by immunohistochemistry in 78 ACC samples and 5 normal adrenals using a tissue array (scoring of expression: 0–3). Finally, the presence of spontaneous survivin-recognizing T-cells in the peripheral blood of 7 ACC patients were investigated by indirect interferon-gamma-ELISPOT using HLA-A1, -A2 or -B35 restricted survivin peptides.

Results: Survivin RNA was detectable in 11/12 ACCs and 8/13 normal adrenals. However, the mean expression in ACC was an order of magnitude higher than in normal adrenals (9071±5561% vs. 100±25%, P<0.001). Immunohistochemistry confirmed survivin protein expression in 89% of ACCs. Moreover, in 38/78 of the ACCs but in none of the normal adrenals the expression was judged as moderate-to-high (score 2 or 3). Notably, in 1/7 ACC patients spontaneous HLA-A2-restricted survivin-specific T cells response was detected suggesting that the used epitope might be of immunotherapeutic value.

Conclusion: This is the first study addressing survivin expression in a large series of ACC patients. Since antiapoptotic survivin is overexpressed in many ACCs and exhibits immunogenic properties, it is an intriguing target for immunotherapy also in this rare disease. Especially in patients with refractory ACC having progressed after several cytotoxic therapies an experimental vaccination approach seems to be justified and promising.