ecancermedicalscience

Research

EpCAM expression negatively regulates E-cadherin function in colorectal carcinomas

6 Jul 2023
Uchenna Simon Ezenkwa, Gabriel Olabiyi Ogun, Mbwas Isaac Mashor, Olufemi John Ogunbiyi

Background: This study aimed to characterise epithelial cell adhesion molecule (EpCAM) expression patterns in colorectal carcinomas (CRC) from Nigerian patients, its association with E-cadherin and tumour characteristics, to forecast patient selection for anti-EpCAM therapy among whom no data existed previously.
Methods: Tissue microarray blocks of formalin-fixed and paraffin-embedded CRC tissues, with their non-cancer margins of resection, were sectioned and stained with EpCAM and E-cadherin primary antibodies. Scoring for antibody staining was done semiquantitatively by combining staining proportion and intensity. The outcome was correlated with patient age, gender and tumour histological parameters with p ≤ 0.05 regarded as statistically
significant.
Results: Sixty-three carcinoma tissues had staining status for the two markers and were included in this study. Of these, 36 (57.1%) showed positive EpCAM expression (immunoscore ≥3) out of which 83% (30/36 positive cases) were overexpressed (combined immunoscore ≥4) while 12 (19%) tissues were positive for E-cadherin. Non-tumour margins of resection tissues showed less EpCAM positivity in 24% (6/25) of histospots. The difference in staining between tumour and non-tumour margin tissues with EpCAM was significant (p < 0.001). Also, EpCAM  overexpression was significantly associated with reduced E-cadherin (p < 0.035) expression in tumour cells. Tumour extent within the gut wall was equal (50% each) for early and late pT stages among EpCAM overexpressing tumours but two-thirds (8/12) of cases expressing E-cadherin had later pT stage paradoxically, while distant metastasis was negligible among tumours bearing both markers. Also, tumours overexpressing EpCAM had significant association with tumour-associated lymphocytes (p < 0.02 each).
Conclusion: CRC in this study preferentially overexpress EpCAM over E-cadherin whose strong cell-cell contact inhibitory role is weakened even when expressed, resulting in further local tumour spread. This, and the observed immune response, supports targeted therapy among eligible patients
 

Related Articles

Ajay Kumar Yadav, Anshuman Pandey, Rahul Singh, Hareesh Shanthappa Nellikoppad, Bhanu Pratap Singh
Charles M Balch, Ning Liao, Dennis S C Lam, Jeffrey N Weitzel, Rui-Hua Xu, Gerhardt Attard, Paul A Bunn, Alexander M M Eggermont, Jie He, Yuko Kitagawa, Soon Thye Lim, Eduardo Cazap, Bernard Esquivel, Xianqun Fan, Louis W C Chow, Edward S F Liu, Hector Martinez Said, John E Niederhuber, Isabel T Rubio, Ashraf Saad Zaghloul, Oscar G Arrieta, Riccardo A Audisio, Geerard L Beets, Felipe J F Coimbra, Jorge E Gallardo, Judy E Garber, Alessandro Gronchi, Volker Heinemann, Allison W Kurian, Miriam Mutebi, Masaki Mori, Funmi I Olopade, Piotr Rutkowski, Mansoor Saleh, William M Sanchez, Raymond Sawaya, John F Thompson, Gerald Tumusiime, Carlos S Vallejos, David C Whiteman, YiLong Wu, King-David T Yawe, Nayef Awad Al Zahrani, Odysseas Zoras, Banu K Arun, Carol J Fabian, Jeffrey E Gershenwald, William J Gradishar, Jin He, V Suzanne Kimberg, Ronald M K Lam, Victor H F Lee, Domenica Lorusso, Tony S K Mok, N D Perrier, Hope S Rugo, Cornelia Ulrich, Chandrakanth Are, J Vignat, I Soerjomataram
Yousef Roosta, Hero Khezri, Vahid Hoseinpour, Mohamad Jebraeily, Amirhossein Rayegani, Saeed Razavi-Dizaji
Josepmilly Del Valle Peña Colmenares, Wladimir José Villegas Rodríguez, Osama Bahsas Zaky, Carlos Eduardo Martínez, Douglas José Angulo Herrera