Eph A2 promotes tumor growth, invasiveness and angiogenesis in mCRC. Targeting Eph A2 could overcome resistance to anti-epidermal growth factor receptor treatment in colon cancer preclinical models.
Formalin-fixed paraffin-embedded tumor specimens from 82 RAS wild type (WT) mCRC pts treated with cetuximab + FOLFIRI as first line therapy in the CAPRI GOIM trial were assessed for Eph A2 expression by immunohistochemistry. Eph A2 levels were evaluated developing an HSCORE [1 × (% cells 1+) + 2 × (% cells 2+) + 3 × (% cells 3+)] (range: 0-300). A cut off was set by ROC analysis to define high (>50) and low (≤50) Eph A2 levels.
Eph A2 expression was found in 55/82 (67%) cases. According to HSCORE Eph A2 levels were low in 54 (66%) and high in 28 (34%) samples. Eph A2 expression resulted in mostly complete membranous staining. Tumor stroma was positive in 15/82 (18%) cases. In most of these cases an intense immune infiltrate was observed. Non-tumor adjacent normal mucosa was assessable in 34/82 samples. Eph A2 was expressed in 16/34 (47%), more frequently in dysplastic epithelial areas. A significant correlation between Eph A2 expression in tumor and stroma was found (p
Eph A2 levels were significantly associated with a worse PFS and an increase in PD in RAS WT mCRC pts treated with cetuximab + FOLFIRI as first line therapy in the CAPRI GOIM trial, in both right- and left-sided tumors. A similar trend was observed for OS. Eph A2 might represent an additional predictive biomarker of lack of efficacy in RAS WT mCRC pts treated with cetuximab + FOLFIRI.
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Department of Clinical and Experimental Medicine ‘F. Magrassi’ Università degli studi della Campania “Luigi Vanvitelli”, Naples, Italy.
F. Ciardiello: Advisory boards: Merck Serono, Lilly, Roche, Bayer, Amgen, Pfizer. E. Martinelli: Advisory boards: Merck Serono, Amgen. All other authors have declared no conflicts of interest.