ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2008) 16 P308

ERCC1 expression in adrenocortical carcinoma: relationship with baseline characteristics and response to platinum-based chemotherapy

Cristina L Ronchi3, Silviu Sbiera1, Patrick Adams2, Luthgard Kraus1, Heidi Linss1, Sebastian Wortmann1, Holger Willenberg4, Bruno Allolio1 & Martin Fassnacth1

1Endocrine and Diabetes Unit, Department of Medicine I, University of Wuerzburg, Wuerzburg, Germany; 2Institute of Pathology; University of Wuerzburg, Wuerzburg, Germany; 3Endocrine Unit, Department of Medical Sciences, Fondazione IRCCS Ospedale Maggiore Policlinico and University of Milan, Milan, Italy; 4Department of Endocrinology, University of Duesseldorf, Duesseldorf, Germany.

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: 1.1–5.5, 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.