2005 - Development of novel diagnostic markers for bile duct cancer 


Stephen PereiraDr Steve Pereira
Based: Royal Free & University College London Medical School
Donor: Brian Mercer Charitable Trust Amount: £107,170 (payable over two years)
Start date: 1st August 2005 
 
Title of study: Development of novel diagnostic markers for bile duct cancer    

Download the lay summary of this research: Lay Review Pereira.pdf 

Project 1: Diagnosis of pancreaticobiliary malignancy by detection of minichromosome maintenance 5 protein (Mcm 5) in bile aspirates  

Results: The expression of mcm protein in bile duct cancer tissues was 12 times greater than in benign strictures or normal bile duct tissues. Moreover, no benign tissue sample had levels of Mcm protein higher than a cancer case, suggesting that this protein may be a very accurate diagnostic marker of cancer. In bile, the Mcm5 test was four times more sensitive than standard biliary brush cytology (66% vs. 20%) in detecting bile duct cancer.  

Conclusions: In this pilot study we have shown for the first time that the Mcm5 test in bile is superior to standard biliary brush cytology in detecting bile duct cancer. The manuscript has now been submitted for publication and we are planning a larger follow-up study to confirm these exciting results.  

The manuscript of this project was published in the prestigious British Journal of Cancer in Spring 2008.    

Download: Diagnosis of pancreaticobiliary malignancy by detection of minichromosone maintenance protein 5 in bile aspirates

Project 2: MUC4 and MUC5AC are highly specific tumour-associated mucins in biliary tract cancer  

Results: Both mucins, MUC4 in bile and MUC5AC in blood, were exclusively expressed in patients with biliary tract cancer or the potentially pre-cancerous condition primary sclerosing cholangitis and were highly diagnostic for cancer (specificity of 93% for MUC4 and 96% for MUC5AC). This compared well to the ‘best’ currently available blood marker CA19-9, which was falsely positive in more than one third of non-cancerous conditions.  

Conclusions: We have shown for the first time that the mucin MUC4 in bile samples is highly specific for biliary tract cancer. We also confirmed the findings of a previous study from Thailand that MUC5AC in blood is highly specific for biliary tract cancer, which makes MUC4 a potentially useful screening tool for cancer detection and a target for cancer-specific treatments.  

The manuscript of this project was also published in the prestigious British Journal of Cancer in Spring 2008.   

Download: MUC4 and MUC5AC are highly specific tumour-associated mucins in biliary tract cancer