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07-05-2013 | Article

NSCLC cisplastin sensitivity screening ‘limited’

Abstract

Free abstract

medwireNews: Antibody technology is not yet sufficiently sophisticated to allow screening of non-small-cell lung cancer (NSCLC) patients for sensitivity to cisplatin-based chemotherapy, suggests research published in the New England Journal of Medicine.

The study shows that while the 8F1 antibody can accurately detect levels of the excision repair cross complementation group 1 (ERCC1) protein, it is unable to distinguish between the functional isoform associated with repair of platinum-based damage and the three other variants that have no impact on treatment response.

"As a result, its usefulness in guiding therapeutic decision making is limited," say Jean-Charles Soria (INSERM U981, Institut Gustave-Roussy, Villejuif, France) and co-authors, who believe their findings "underscore the importance of assessing multiple isoforms and their function in biomarker studies."

The team used 8F1 antibody immunohistochemistry to measure ERCC1 protein expression in NSCLC samples taken from 494 patients participating in two phase III cisplatin clinical trials. A third set of NSCLC samples taken from 589 participants in the International Adjuvant Lung Cancer Trial (IALT) Biology study - which was the first to examine the correlation between ERCC1 expression and platinum response - were also assessed.

The researchers found no significant difference in the overall survival of patients with ERCC1-negative and -positive tumors for either the cisplastin-treated or control groups.

Nor were the team able to replicate IALT Biology results indicating that immunostaining for ERCC1 significantly predicted response and patient survival. Indeed, they suggest that the 8F1 antibody performance may have altered since the original study in 2006 due to the significant difference in results between that study and their current study.

"Undisclosed characteristics of the antibody might have changed its specificity over the years, and the differences between the two 8F1 batches could be related to distinct antibody titration, affinity, purity, or even epitope recognition," Soria et al note.

Furthermore, as all of the 16 commercially available ERCC1 antibodies tested were able to bind to at least three of the four isoforms, none could discriminate between the fully functional ERCC1-202 isoform associated with cisplatin resistance and the other forms.

"Our results show that ERCC1 isoform transcripts and proteins are heterogeneously expressed in cell lines and tumor samples," the team concludes.

"It is therefore crucial to characterize their respective functionality with regard to repair of platinum-DNA adducts in order to avoid misclassification of tumors expressing a high level of nonfunctional ERCC1."

medwireNews (www.medwirenews.com) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2013

By Lynda Williams, Senior medwireNews Reporter