Abstract 4901
Background
A tumour suppressive role for EPHB receptors in various malignancies has been described, however their expression profile and prognostic significance in human colorectal cancers (CRCs) remain unclear. In this study, we aimed to investigate the expression profile of EPHB3 during CRC progression and determined its prognostic impact in a large cohort of CRC samples.
Methods
We examined the EPHB3 mRNA levels by real time PCR with fresh frozen CRC samples and evaluated protein expression by immunohistochemistry with tissue microarrays containing various benign tumours and 610 CRC samples. AOM-DSS induced colitis model was used to investigate the EPHB3 expression profile during the colitis-associated carcinogenesis.
Results
EPHB3 expression was upregulated in CRCs than in normal colonic mucosa, and showed positive correlations with intestinal stem cell (ISC) markers (EPHB2, OLFM4, LRIG1) and CD44, a candidate cancer stem cell marker. EPHB3 positivity was observed in 24% of 610 CRCs and showed negative correlations with differentiation, lympho-vascular invasions and TNM stages. EPHB3 expression significantly declined during adenoma-carcinoma transition and invasion into deeper layers. In particular, a substantial reduction of EPHB3 was observed in the budding cancer cells at the invasive fronts. In AOM-DSS induced colitis-associated colon cancer model, EPHB3 expression increased along with tumor development. Notably, EPHB3 was positively associated with microsatellite instability (MSI) phenotype but was not associated with CpG island methylator phenotype, KRAS and BRAF mutations. Furthermore, EPHB3 positivity was a prognostic marker for better clinical outcomes in CRC patients.
Conclusions
EPHB3 was upregulated in CRCs and showed positive correlations with candidate cancer stem cell marker CD44. EPHB3 expression decreased during adenoma-carcinoma transition and particularly in the budding cancer cells at the invasive fronts. EPHB3 positivity was associated with MSI phenotype and demonstrated to be a good prognostic marker in CRCs.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
5629 - Outcome of triple negative inflammatory breast cancers (TNIBC) treated with dose dense neoadjuvant epirubicin cyclophosphmide, prognostic impact of pre and post neoadjuvant chemotherapy (NAC) tumor infiltrating lymphocytes (TIL) and post NAC lymphovascular invasion
Presenter: Luca Campedel
Session: Poster Display session 2
Resources:
Abstract
5792 - A novel PET parameter for cancer stem cell metabolism: early prediction of chemosensitivity to neoadjuvant chemotherapy in locally advanced breast cancer
Presenter: Chanwoo Kim
Session: Poster Display session 2
Resources:
Abstract
3728 - Using nodal ratio to predict recurrence in patients with 4 or more positive lymph nodes early stage breast cancer
Presenter: Besma Graja
Session: Poster Display session 2
Resources:
Abstract
3395 - Re-sentinel node biopsy for local recurrence after breast-conserving surgery
Presenter: Yuka Matsubara
Session: Poster Display session 2
Resources:
Abstract
4302 - Assessment of prognostic and therapeutic factors in men with breast cancer
Presenter: Daniel Herrero Rivera
Session: Poster Display session 2
Resources:
Abstract
4263 - Genomic Profiling of Chinese Breast Cancer Patients
Presenter: Zhonghua Tao
Session: Poster Display session 2
Resources:
Abstract
2406 - Genome copy number alteration burden represents predictor of response in long-term, never relapse exceptional responders of trastuzumab-treated HER2+ metastatic breast cancer
Presenter: Naomi Walsh
Session: Poster Display session 2
Resources:
Abstract
2575 - Next-generation DNA Sequencing (NGS) Results for Tumors From Phase 2 ABRAZO Study of Talazoparib After Platinum or Cytotoxic Non-Platinum Regimens in Patients (pts) With Advanced Breast Cancer (ABC) and Germline BRCA1/2 (gBRCA) Mutations
Presenter: Nicholas C. Turner
Session: Poster Display session 2
Resources:
Abstract
4499 - FGFR1 and CCND1 gene amplifications are associated with breast cancer resistance to aromatase inhibitors
Presenter: Evgeny Imyanitov
Session: Poster Display session 2
Resources:
Abstract
4110 - Clinicopathologic features of BRCA mutated breast cancer patients: Hacettepe Experience
Presenter: Sercan Aksoy
Session: Poster Display session 2
Resources:
Abstract