Telomerase Potential Ca Biomarker

March 1, 2004

This special “annual highlights” supplement to Oncology News International is acompilation of some of the major advances in the management of gastrointestinalcancers during 2003–2004, as reported in ONI. Guest editor Dr. James L. Abbruzzesecomments on the reports included herein and discusses advances in the clinicalmanagement of GI cancers, with a focus on developments in targeted therapy, newcombinations, adjuvant therapy, and what to watch for in 2004.

SEATTLE-Telomerase maybe an early biomarker of pancreatobiliarymalignancies, and telomerase enzymeimmunostaining represents a potentialbreakthrough in screening forand diagnosing cancer in patients withbiliary strictures, Tarun Mullick, MD,said at the president's plenary sessionof the 67th Annual Meeting of theAmerican College of Gastroenterology(ACG abstract 3).Current methods of screening forand diagnosing cholangiocarcinomasare inadequate, with endoscopic retrogradecholangiopancreatography(ERCP) brush cytology only 30% to70% effective, Dr. Mullick said in aninterview with ONI."But having abiomarker may enhance your techniqueto something that is closer to90% to 100% sensitive. Using a biomarkeris such a leap in concept; this isthe first real study that looked at thepossibility of doing this."Telomerase is a reverse transcriptase.It synthesizes telomericDNA, and its upregulation confersimmortality to cancer cells, said Dr.Mullick, instructor of clinical internalmedicine, Division of Gastroenterol-ogy and Hepatology, University ofVirginia, Charlottesville.At the ACG meeting, Dr. Mullickand his colleagues presented preliminarydata on telomerase as a potentialbiomarker of cancer. These preliminaryfindings showed that 15 of 15pancreatobiliary malignancies, includingtwo cholangiocarcinomas, weretelomerase positive, while 5 of 5 be-nign pancreatic ducts were telomerasenegative.In the current study, the investigatorssought to determine the role oftelomerase in differentiating benignbile ducts from cholangiocarcinomain surgical resection specimens,and to determine the feasibility of utilizingtelomerase enzyme detectionwith ERCP brush cytology in patientswith benign and malignant biliarystrictures.Telomerase staining was performedon surgical resection specimens from10 patients with cholangiocarcinomaand 10 with benign bile ducts. Theresearchers also assessed for telomeraseenzyme in seven patients withbiliary stricture-four who progressedto or were diagnosed with cancer andthree with benign ducts-using ERCPbrush cytology.Dr. Mullick explained that telomeraseantibody immunostaining is performedby first deparaffinizing andrehydrating tissues, and then retrievingthe telomerase enzyme antigen.Primary and secondary antibody incubationare then performed, and theenzyme is visualized using AEC chromagen,which stains brown/red.Of the 14 patients with cholangiocarcinoma,all were found to be telomerasepositive. The 13 patients withbenign bile ducts were all telomerasenegative. There were no significantdifferences between the patients withmalignancies and those with benignducts regarding age, sex, primary sclerosingcholangitis (PSC), length of historyof PSC, colorectal cancer, andulcerative colitis. Tumor stage and locationalso did not affect the level oftelomerase expression."In this particular cohort, we cansay that positive telomerase expressionmay differentiate cholangiocarcinomafrom benign bile duct andmerits further evaluation as a potentialmethod to screen for and diagnosecholangiocarcinoma," Dr. Mullicksaid.He noted that telomerase enzymeassay may become useful in ERCPbrush cytology to help differentiatecholangiocarcinoma from benign bileducts, "but this, of course, needs to befurther validated with a larger numberof patients, and the technique has tobe improved."Other key investigators in the studyincluded Jason Tasch, PhD, DarwinConwell, MD, and Gregory Zuccaro,Jr., MD, of the Cleveland Clinic Foundation;Paul Yeaton, MD, of the Universityof Virginia; and Adrian Ormsby,MBBS, of the Henry Ford Institute,Detroit.