Abstract 2853: Epidermal growth factor receptor (EGFR) and prostaglandin-endoperoxide synthase 2 (PTGS2) are prognostic biomarkers for metastatic colorectal cancer
Authors: Goos Jeroen A.C.M. , Hiemstra Annemieke C. , Coupé Veerle M.H. , Diosdado Begoña , Kooijman Wendy , Diemen Pien M. Delis-van , Karga Cemile , Beliën Jeroen A.M. , Oordt C. Willemien Menke-van der Houven van , Geldof Albert A. , Meijer Gerrit A. , Hoekstra Otto S. , Fijneman Remond J.A. 
Published: May 2015

Background: Resection of colorectal cancer liver metastasis (CRCLM) with curative intent is beneficial in approximately 30% of cases, indicating the need for prognostic biomarkers to improve clinical management of CRCLM patients. Protein expression levels of epidermal growth factor receptor (EGFR) and prostaglandin-endoperoxide synthase 2 (PTGS2; also known as cyclooxygenase-2 or COX2) have been associated with carcinogenesis, metastases and survival. EGFR and PTGS2 are targets for molecular drugs and exhibit complex molecular interactions.

Aim: We aimed to determine the prognostic value of EGFR and PTGS2 expression in CRCLM of patients who underwent liver resection.

Patients and methods: Formalin-fixed paraffin-embedded CRCLM tissue and corresponding primary tumor specimens from a multi-institutional cohort of patients who underwent liver resection between 1990 and 2010 were incorporated into tissue microarrays (TMAs). TMAs were stained for EGFR and PTGS2 by immunohistochemistry and a hazard rate ratio (HRR) for the association between expression in CRCLM and overall survival (OS) was calculated. Results were validated by 500-fold cross-validation.

Results: EGFR expression could be evaluated in 323 patients and PTGS2 expression in 351 patients. EGFR expression in CRCLM was associated with poor prognosis in both univariate analysis (average HRR 1.47; P=0.03) and multivariate analysis with standard clinicopathological prognostic variables (average HRR 1.54; P=0.02). PTGS2 expression was also associated with poor prognosis in both univariate (average HRR 1.63; P&lt;0.01) and multivariate analysis (average HRR 1.59; P=0.01). Stratification for systemic therapy demonstrated prognostic value for EGFR and PTGS2 only in the subgroup of patients who were not treated (HRR 1.78; P&lt;.01 and HRR 1.64; P=0.04, respectively), with worst prognosis when both EGFR and PTGS2 were highly expressed (HRR 3.08; P&lt;.01). CRCLM expression of PTGS2 was concordant in 69.2% of matched primary tumors (P=0.02), while there was no such correlation for EGFR expression (P=0.51).

Conclusion: EGFR and PTGS2 expression are prognostic molecular biomarkers with added value to standard clinicopathological variables for patients with CRCLM.

Citation Format: Jeroen A.C.M. Goos, Annemieke C. Hiemstra, Veerle M.H. Coupé, Begoña Diosdado, Wendy Kooijman, Pien M. Delis-van Diemen, Cemile Karga, Jeroen A.M. Beliën, C. Willemien Menke-van der Houven van Oordt, Albert A. Geldof, Gerrit A. Meijer, Otto S. Hoekstra, Remond J.A. Fijneman. Epidermal growth factor receptor (EGFR) and prostaglandin-endoperoxide synthase 2 (PTGS2) are prognostic biomarkers for metastatic colorectal cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2853. doi:10.1158/1538-7445.AM2014-2853