Abstract

5528 Background: Human papilloma virus infection (HPV) is a powerful prognostic biomarker in LASCCHN and can be indirectly identified by p16 immunohistochemistry (IHC). Increased EGFR gene copy number has been reported to be a negative predictor of outcome in LASCCHN. In this study the relationship of p16 to EGFR gene copy number in patients treated with chemoradiation was assessed. Methods: Formalin-fixed paraffin embedded tissue was obtained from 110 patients with LASCCHN treated on three clinical trials with conventional chemoradiation or with a tirapazamine containing regimen. EGFR gene copy number was assessed by Fluorescence in situ hybridization (FISH) using LSI EGFR SpectrumOrange/CEP 7 SpectrumGreen probes (Vysis/Abbott). Tumors with high polysomy or amplification of EGFR were scored as positive. p16 was assessed by IHC using a validated antibody (Neomarkers). Markers were correlated with outcome i.e., failure-free survival (FFS) and overall survival (OS) using Cox regression, adjusting for trial. Results: Results for both EGFR FISH and p16 IHC were obtained in 97 patients. EGFR FISH was positive in 21/97 (22%) tumors including 12/66 (18%) oropharyngeal tumors. p16 was positive in 40/97 (41%) tumors including 36/66 (55%) oropharyngeal tumours. Only 1/40 p16 positive tumors were EGFR FISH positive compared with 20/57 p16 negative tumors (p<0.001). EGFR FISH positivity was associated with inferior FFS (HR 2.48 (95%CI 1.14 to 5.38), p = 0.022) and OS (HR 2.33 (95%CI 0.98 to 5.57), p = 0.057). p16 positivity was associated with improved FFS (HR 0.19 (95%CI 0.07 to 0.56), p = 0.002) and OS (HR 0.18 (95%CI 0.05 to 0.62), p = 0.006). On multivariable Cox regression analysis only p16 was independently predictive of outcome (p = 0.007 and 0.0014 for FFS and OS respectively). Conclusions: EGFR FISH positivity and p16 expression were found to be almost mutually exclusive in LASCCHN with only 1 of 97 tumors positive for both markers suggesting that increased EGFR copy number is largely restricted to HPV-negative LASCCHN. EGFR FISH and p16 were predictive of outcome in univariate analyses, but only p16 remained predictive on multivariable analysis. No significant financial relationships to disclose.

Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call