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
3875 - Correlation of radiotherapy with the prognosis of elderly patients with hormone receptor-positive breast cancer according to immunohistochemical subtyping
Presenter: Jin Zhang
Session: Poster Display session 2
Resources:
Abstract
5793 - Real world treatment sequencing patterns in secondary breast cancer (SBC): Pathway visualisation using national datasets.
Presenter: Ashley Horne
Session: Poster Display session 2
Resources:
Abstract
3185 - Utilization Pattern of Bone Targeting Agents in Patients with Solid Tumor in Taiwan, Hong Kong and Korea
Presenter: Shi Jie Lai
Session: Poster Display session 2
Resources:
Abstract
3705 - Clinico-pathological Features and Prognosis of Patients with Pregnancy Associated Breast Cancer – A Matched Case Control Study
Presenter: Ruyan Zhang
Session: Poster Display session 2
Resources:
Abstract
1421 - TRYbeCA-2: A Randomized Phase 2/3 Study of Eryaspase in Combination with Gemcitabine and Carboplatin Chemotherapy versus Chemotherapy Alone As First-Line Treatment in Patients with Metastatic or Locally Recurrent Triple-Negative Breast Cancer
Presenter: Ahmad Awada
Session: Poster Display session 2
Resources:
Abstract
4119 - CONTESSA TRIO: A Multinational, Multicenter, Phase 2 Study of Tesetaxel plus 3 Different PD-(L)1 Inhibitors in Patients with Metastatic Triple-Negative Breast Cancer (TNBC) and Tesetaxel Monotherapy in Elderly Patients with HER2- Metastatic Breast Cancer (MBC)
Presenter: Sara Tolaney
Session: Poster Display session 2
Resources:
Abstract
4545 - Bintrafusp alfa (M7824) and Eribulin Mesylate in Treating Patients With Metastatic Triple Negative Breast Cancer (TNBC)(NCT03579472)
Presenter: Jennifer Litton
Session: Poster Display session 2
Resources:
Abstract
3340 - Effectiveness of Olaparib Plus Trastuzumab in HER2[+], BRCA–mutated (BRCAm) or Homologous Recombination Deficient (HRD) Advanced Breast Cancer (ABC) patients (pts). The OPHELIA Study
Presenter: José Enrique Alés-Martínez
Session: Poster Display session 2
Resources:
Abstract
1113 - RIBOB : A Study on the efficacy and safety of Ribociclib in combination with letrozole in Older women (≥70 years) with hormone receptor-positive (HR+) HER2-negative (HER2-) advanced Breast cancer (aBC) with no prior systemic therapy for advanced disease
Presenter: Cindy Kenis
Session: Poster Display session 2
Resources:
Abstract
4025 - RIbociclib plus Goserelin with Hormonal Therapy versus physician Choice chemotherapy in premenopausal or perimenopausal patients with HR+, HER2– inoperable locally advanced or metastatic breast cancer – RIGHT Choice study
Presenter: Nagi El Saghir
Session: Poster Display session 2
Resources:
Abstract