Adrenocortical carcinoma (ACC) is a malignant tumor with poor prognosis and no established therapy in advanced stage. Cisplatin is the most frequently used cytotoxic drug, but even combined with doxorubicin and etoposid, the response rate is <50%. Recently, it has been demonstrated that the excision repair cross complementing group 1 (ERCC1) plays a relevant role in the DNA repairing process, particularly in the correction of platinum-induced DNA adducts. Accordingly, ERCC1 expression predicted prognosis in patients with different types of cancers when treated with platinum-compounds. In this study, we evaluated the expression of ERCC1 by immunohistochemistry in ACC and correlated it with clinical outcome. We evaluated 170 adrenal tumor samples spotted on three tissue microarrays, comprising 15 benign tumors (5 inactive, 5 cortisol producing and 5 aldosterone producing adenomas) and 155 ACCs. ERCC1 protein was highly expressed in 14 benign tumors (93%) and only in 71 ACCs (46%, P<0.005). No differences in baseline clinical or histological parameters were found between ACC patients with high and low ERCC1 staining. No impact of ERCC1 expression on overall or disease-free survival was observed in patients who did not receive platinum-based chemotherapy. However, ERCC1 expression was associated with clinical outcome in patients treated with platinum-based regimens (n=36). Two of 17 positive patients had a partial response to treatment, while 4 of the 19 negative patients experienced a partial (n=3) or a complete response (n=1). In univariate analysis, ERCC1 expression was the only significant predictor of survival after first platinum administration (median survival: 7 months in positive versus 17 months in negative patients, HR: 2.1, 95% CI: 1.15.5, P<0.05). In conclusion, ERCC1 expression may be a novel prognostic factor for predicting survival in ACC patients treated with platinum-based chemotherapy and may provide critical information for individualized treatment.
03 - 07 May 2008
European Society of Endocrinology