The Significance of Co-Expression of Epidermal Growth Factor Receptor (EGFR) and Ki67 on Clinical Outcome in Patients with Anal Cancer Treated with Chemoradiotherapy: An Analysis of Study XXXX

Publication date: Available online 23 November 2016
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Corinne M. Doll, Jennifer Moughan, Alexander Klimowicz, Clement K. Ho, Elizabeth N. Kornaga, Susan P. Lees-Miller, Jaffer A. Ajani, Christopher H. Crane, Lisa A. Kachnic, Gordon S. Okawara, Lawrence B. Berk, Kevin S. Roof, Mark J. Becker, David L. Grisell, Robert J. Ellis, Paul Sperduto, Gerald Marsa, Chandan Guha, Anthony Magliocco
PurposeTo measure co-expression of EGFR and Ki67 proteins in pre-treatment tumor biopsies of anal cancer patients enrolled on Study XXXX, a phase III trial comparing 5FU/MMC/RT (Arm A) vs. 5FU/cisplatin/RT (Arm B), and to correlate expression with clinical outcome.Materials/MethodsEGFR and Ki67 co-expression was measured after constructing a tissue microarray using fluorescence immunohistochemistry and automated quantitative image analysis (AQUA). Ki67 score within EGFR high vs. low areas (Ki67ratio in EGFRhigh:low) in each tumor core was analyzed at the median, quartiles and as a continuous variable. Associations between the tumor markers and clinical endpoints [overall and disease-free survival (OS, DFS), loco-regional and colostomy failure (LRF, CF), and distant metastases (DM] were explored.Results282 pre-treatment tumors were analyzed from Study XXXX. Of evaluated specimens, 183 (65%, n=89, Arm A; n=94, Arm B) were eligible and analyzable. There were no significant differences in baseline characteristics or outcomes between analyzable and unanalyzable patient cases. Median follow-up was 6.0 years. On multivariate analysis, after adjusting for gender, patients with Ki67ratio in EGFRhigh:low ≥ median had worse OS (HR=2.41, 95% C.I. = [1.38, 4.19], p=0.0019). After adjusting for N stage and largest tumor dimension, patients with Ki67ratio in EGFRhigh:low ≥ median had a higher risk of a disease-free failure (HR=1.85, 95% C.I. = [1.18, 2.92], p=0.0078). Technical validation with an independent anal cancer patient cohort was performed and shows a very similar biomarker score distribution.ConclusionsHigh Ki67ratio in EGFRhigh:low is associated with worse clinical outcome in this subset of patients with anal cancer treated with chemoradiation on Study XXXX. Evaluation within a clinical trial will be required to determine whether patients with these tumor characteristics may specifically benefit from an EGFR targeted therapeutic agent.

Teaser

Co-expression of EGFR and Ki67 was measured in pre-treatment tumor biopsies of anal cancer patients enrolled on Study XXXX. It was determined those patients whose tumors had Ki67ratio in EGFRhigh:low ≥ median had worse overall survival and disease-free survival. This suggests that proliferative dysregulation in EGFR high expressing tumor cells is a potential marker of aggressiveness.


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