ERCC1 as predictive biomarker to platinum-based chemotherapy in adrenocortical carcinomas

Research output: Contribution to journalArticle

Authors

  • Valeria Laufs
  • Barbara Altieri
  • Silviu Sbiera
  • Stefan Kircher
  • Sonja Steinhauer
  • Felix Beuschlein
  • Marcus Quinkler
  • Holger S Willenberg
  • Andreas Rosenwald
  • Martin Fassnacht

Colleges, School and Institutes

External organisations

  • Division of Endocrinology and Diabetes, Department of Internal Medicine I, University Hospital, University of Wuerzburg
  • Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Wuerzburg, Wuerzburg, Germany.

Abstract

Objective Platinum-based chemotherapy (PBC) is the most effective cytotoxic treatment for advanced adrenocortical carcinoma (ACC). Excision repair cross complementing group 1 (ERCC1) plays a critical role in the repair of platinum-induced DNA damage. Two studies investigating the role of ERCC1 immunostaining as a predictive marker for the response to PBC in ACC had reported conflicting results. Both studies used the ERCC1-antibody clone 8F1 that later turned out to be not specific. The aim of this study was to evaluate the predictive role of ERCC1 with a new specific antibody in a larger series of ACC.

Design and methods 146 ACC patients with available FFPE slides were investigated. All patients underwent PBC (median cycles = 6), including cisplatin (n = 131) or carboplatin (n = 15), in most cases combined with etoposide (n = 144), doxorubicin (n = 131) and mitotane (n = 131). Immunostaining was performed with the novel ERCC1-antibody clone 4F9. The relationship between ERCC1 expression and clinicopathological parameters, as well as best objective response to therapy and progression-free survival (PFS) during PBC was evaluated.

Results High ERCC1 expression was observed in 66% of ACC samples. During PBC, 43 patients experienced objective response (29.5%), 49 stable disease (33.6%), 8 mixed response (5.5%) and 46 progressive disease (31.5%) without any relationship with the ERCC1 immunostaining. No significant correlation was also found between ERCC1 expression and progression-free survival (median 6.5 vs 6 months, P = 0.33, HR = 1.23, 95% CI = 0.82–2.0).

Conclusion ERCC1 expression is not directly associated with sensitivity to PBC in ACC. Thus, other predictive biomarkers are required to support treatment decisions in patients with ACC.

Details

Original languageEnglish
Pages (from-to)181-188
JournalEuropean Journal of Endocrinology
Volume178
Early online date29 Nov 2017
Publication statusPublished - Feb 2018