[1264] Comparison and Clinical Validation of Three ERCC1 Antibodies in Head and Neck Squamous Cell Carcinoma (HNSCC)

Melissa C Austin, Brenda F Kurland, Renato G Martins, Julie E Bauman, Rodney A Schmidt. University of Washington Medical Center, Seattle, WA; Fred Hutchinson Cancer Research Center, Seattle, WA; University of Pittsburgh Cancer Institute, Pittsburgh, PA

Background: The DNA repair endonuclease excisional cross-complementing group 1 (ERCC1) protein is crucial for repair of interstrand crosslinks induced by platinum chemotherapy. ERCC1 expression predicts clinical benefit from platinum chemotherapy in non-small cell lung cancer and HNSCC, but the specificity of the [8F1] antibody used in the original studies has been questioned. Because new reagents have become available, we evaluated three ERCC1 antibodies for prognostic utility and ease of interpretation.
Design: Optimized immunohistochemistry (IHC) conditions were established against controls for Neomarkers [8F1], OriGene [4F9], and Santa Cruz [FL297] antibodies. IHC was performed on 90 pre-treatment biopsy samples in patients with HNSCC subsequently treated with cisplatin-radiotherapy. ERCC1 expression was described by H-score (weighted percentage of cells demonstrating nuclear staining x staining intensity). The primary endpoint was ability to predict progression free survival (PFS) with a secondary endpoint of qualitative ease of interpretation.
Results:

ERCC1 Expression by Antibody
AntibodyNDecreased/Normal (H<2.25)Increased (H>2.25)
[8F1]9048 (53%)42 (47%)
[4F9]8840 (46%)48 (54%)
[FL297]8848 (55%)40 (45%)




The [4F9] antibody demonstrates the crispest nuclear staining.


Conclusions: We found no correlation between [8F1] expression and PFS, but decreased expression by [4F9] and [FL297] antibodies correlated with better PFS, consistent with previous reports that ERCC1 predicts platinum benefit in HNSCC. Nuclear reactivity was the critical interpretive endpoint. The crisp nuclear reactivity of the [4F9] antibody makes it easiest to interpret; thus, it may be preferred for clinical development.
Category: Head & Neck

Wednesday, March 6, 2013 9:30 AM

Poster Session V # 199, Wednesday Morning

 

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