Heterogeneity of epidermal growth factor receptor (EGFR) expression and variation in immunohistochemistry (IHC) testing may affect access to EGFR-targeted therapy in patients with advanced colorectal cancer (CRC)

Abstract

10104 Introduction: Cetuximab, an IgG1 MAb directed at the EGFR, has demonstrated benefit in pts with CRC and is currently indicated in EGFR expressing CRC. However, previous reports show heterogeneous EGFR expression between anatomic sites and suggest that results from IHC testing vary between labs. To assess this variability and the resultant impact on pt access to EGFR-targeted therapy, we compared EGFR results reported to clinicians by hospital and reference labs with those obtained at a single central lab. Methods: Formalin-fixed, paraffin-embeded CRC specimens submitted through the Targeted Diagnostics Advocacy Program (tdap) were assayed using the Dako EGFR pharmDx kit and scored using the FDA-approved package insert. If the initial specimen tested EGFR negative (−), additional specimens were requested for assay. Prior EGFR results, lab, and specimen ID were documented through review of anatomic pathology reports. Results: Of 332 evaluable CRC pts tested, 245 pts (74%) were previously reported as EGFR(−). After retesting, 167 (68%) pts were found to be EGFR The originally tested tumor block was retested in 82 pts and 41 pts (50%) were found to be EGFR (+). Retest results were similar for both hospital and reference labs. Of 66 pts with >1 specimen from the same anatomic site tested, 21 (32%) were discordant (at least 1 (+) and one (−) result). Results from different anatomic sites were compared for 65 pts, 34 (52%) of which were discordant (+). Overall, 231 pts (70%) tested EGFR(+). Conclusion: This study shows marked heterogeneity in EGFR expression by IHC both within and across anatomic sites from the same pt as well as variability in both hospital and reference pathology labs. This variability undoubtedly has an adverse impact on pt access to EGFR-targeted therapy. The impact of EGFR heterogeneity may be reduced through the assay of multiple specimens. [Table: see text] [Table: see text]