Journal of Pathology and Translational Medicine

Original Articles

Prognostic Significance of EPHB2 Expression in Colorectal Cancer Progression: Bo Gun Jang, Hye Sung Kim, Weon Young Chang, Jeong Mo Bae, Gyeong Hoon Kang; J Pathol Transl Med. 2018;52(5):298-306. Published online July 18, 2018; DOI: https://doi.org/10.4132/jptm.2018.06.29

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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.

Citations

Citations to this article as recorded by

Potential role of the Eph/ephrin system in colorectal cancer: emerging druggable molecular targets
João Figueira Scarini, Moisés Willian Aparecido Gonçalves, Reydson Alcides de Lima-Souza, Luccas Lavareze, Talita de Carvalho Kimura, Ching-Chu Yang, Albina Altemani, Fernanda Viviane Mariano, Heloisa Prado Soares, Gary Chris Fillmore, Erika Said Abu Egal
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Comprehensive pan-cancer analysis reveals EPHB2 is a novel predictive biomarker for prognosis and immunotherapy response
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Aurora Kinase A Is a Prognostic Marker in Colorectal Adenocarcinoma: Hyun Min Koh, Bo Geun Jang, Chang Lim Hyun, Young Sill Kim, Jin Won Hyun, Weon Young Chang, Young Hee Maeng; J Pathol Transl Med. 2017;51(1):32-39. Published online December 25, 2016; DOI: https://doi.org/10.4132/jptm.2016.10.17

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24 Web of Science
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Abstract PDF

Background
Aurora kinase A (AURKA), or STK15/BTAK, is a member of the serine/threonine kinase family and plays important roles in mitosis and chromosome stability. This study investigated the clinical significance of AURKA expression in colorectal cancer patients in Korea.
Methods
AURKA protein expression was evaluated by immunohistochemistry in 151 patients with colorectal adenocarcinoma using tissue microarray blocks. We analyzed the relationship between clinicopathological characteristics and AURKA expression. In addition, the prognostic significance of various clinicopathological data for progression-free survival (PFS) was assessed. Also we evaluated copy number variations by array comparative genomic hybridization and AURKA gene amplification using fluorescence in situ hybridization in colorectal carcinoma tissues.
Results
AURKA gene amplification was found more frequently in the 20q13.2–13.33 gain-positive group than the group with no significant gain on the AURKA-containing locus. AURKA protein expression was detected in 45% of the cases (68/151). Positive staining for AURKA was observed more often in male patients (p = .035) and distally located tumors (p = .021). PFS was shorter in patients with AURKA expression compared to those with low-level AURKA expression (p < .001). Univariate analysis revealed that AURKA expression (p = .001), age (p = .034), lymphatic invasion (p = .001), perineural invasion (p = .002), and TNM stage (p = .013) significantly affected PFS. In a multivariate analysis of PFS, a Cox proportional hazard model confirmed that AURKA expression was an independent and significant prognostic factor in colorectal adenocarcinoma (hazard ratio, 3.944; p < .001).
Conclusions
AURKA could serve as an independent factor to predict a poor prognosis in Korean colorectal adenocarcinoma patients.

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