title: Expression of excision repair cross complementing group 1 and prognosis in adrenocortical carcinoma patients treated with platinum-based chemotherapy.
abstract: Therapeutic progress in adrenocortical carcinoma (ACC) is severely hampered by its low incidence. Platinum-based chemotherapies are the most effective cytotoxic treatment regimens in ACC but response rates remain <50%. In other tumor entities, expression of excision repair cross complementing group 1 (ERCC1) predicts resistance to platinum compounds. Therefore, we correlated ERCC1 protein expression and clinical outcome. We have retrolectively established adrenal tissue microarrays and analyzed prospectively samples from 163 ACCs, 15 benign adrenal adenomas, and 8 normal adrenal glands by immunohistochemistry for ERCC1 protein expression. Detailed clinical data were available by the German ACC Registry. ERCC1 protein was highly expressed in all normal adrenal glands, 14 benign tumors (93%) and in 75 ACCs (47%). In ACC, no differences in baseline parameters were found between patients with and without ERCC1 expression. Detection of ERCC1 was not correlated with survival in patients who never received platinum-based chemotherapy. In platinum-treated patients (n=45), objective response to platinum compounds was observed in 3/21 patients (14.3%) with high ERCC1 expression and in 7/24 patients (29.2%) with low ERCC1 expression (P=0.23). ERCC1 expression was strongly correlated with overall survival after platinum treatment (median: eight months in patients with high ERCC1 versus 24 months in low ERCC1 expression, hazard ratio (HR) 2.95 (95% confidence interval (CI) 1.4-6.2), P=0.004). Multivariate analysis confirmed that high ERCC1 expression was a predictive factor for poor prognosis in platinum treated patients (HR 2.2, 95% CI 1.0-4.5, P=0.038). Our findings suggest that ERCC1 expression is the first factor for predicting survival in ACC patients treated with platinum-based chemotherapy.
authors.affiliation: Endocrine and Diabetes Unit, Department of Medicine I, University Hospital, University of Würzburg, Josef-Schneider-Strasse 2, 97080 Würzburg, Germany.
authors.forename: Cristina L
authors.initials: CL
authors.lastname: Ronchi
authors.forename: Silviu
authors.initials: S
authors.lastname: Sbiera
authors.forename: Luitgard
authors.initials: L
authors.lastname: Kraus
authors.forename: Sebastian
authors.initials: S
authors.lastname: Wortmann
authors.forename: Sarah
authors.initials: S
authors.lastname: Johanssen
authors.forename: Patrick
authors.initials: P
authors.lastname: Adam
authors.forename: Holger S
authors.initials: HS
authors.lastname: Willenberg
authors.forename: Stefanie
authors.initials: S
authors.lastname: Hahner
authors.forename: Bruno
authors.initials: B
authors.lastname: Allolio
authors.forename: Martin
authors.initials: M
authors.lastname: Fassnacht
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality; D018268:Adrenocortical Carcinoma / Q000175:diagnosis* / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D015331:Cohort Studies; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004720:Endonucleases / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D017671:Platinum Compounds / Q000008:administration & dosage; D011379:Prognosis; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D017671:Platinum Compounds; C071447:ERCC1 protein, human; D004720:Endonucleases