Journal of Pathology and Translational medicine, 2018, 52(5), 298─306, DOI: https://doi.org/10.4132/jptm.2018.06.29

Prognostic Significance of EPHB2 Expression in Colorectal Cancer Progression

Bo Gun Jang, Hye Sung Kim; Weon Young Chang; Jeong Mo Bae; Gyeong Hoon Kang

Abstract

Background: A receptor tyrosine kinase for ephrin ligands, EPHB2, is expressed in normal colorectal tissues and colorectal cancers (CRCs). The aim of this study was to investigate EPHB2 expression over CRC progression and determine its prognostic significance in CRC.
Methods: To measure EPHB2 mRNA and protein expression, real-time polymerase chain reaction and immunohistochemistry were performed in 32 fresh-frozen and 567 formalin-fixed paraffin-embedded CRC samples, respectively. We further investigated clinicopathological features and overall and recurrence-free survival according to EPHB2 protein expression.
Results: The EPHB2 level was upregulated in CRC samples compared to non-cancerous tissue in most samples and showed a strong positive correlation with AXIN2. Notably, CD44 had a positive association with both mRNA and protein levels of EPHB2. Immunohistochemical analysis revealed no difference in EPHB2 expression between adenoma and carcinoma areas. Although EPHB2 expression was slightly lower in invasive fronts compared to surface area (p < .05), there was no difference between superficial and metastatic areas. EPHB2 positivity was associated with lymphatic (p < .001) and venous (p = .001) invasion, TNM stage (p < .001), and microsatellite instability (p = .036). Kaplan–Meier analysis demonstrated that CRC patients with EPHB2 positivity showed better clinical outcomes in both overall (p = .049) and recurrence-free survival (p = .015). However, multivariate analysis failed to show that EPHB2 is an independent prognostic marker in CRCs (hazard ratio, 0.692; p = .692).
Conclusions: Our results suggest that EPHB2 is overexpressed in a subset of CRCs and is a significant prognostic marker.

• DOI: https://doi.org/10.4132/jptm.2018.06.29
• ISBN or ISSN: 2383-7837

• 본 연구는 질병관리본부 연구개발과제(과제번호 2018-보건의료생물자원종합관리) 연구비를 지원받아 수행되었습니다.
• This research was supported by a fund(code 2018-보건의료생물자원종합관리) by Research of Korea Centers for Disease Control and Prevention.