Media Releases

Scientists at Mount Sinai Hospital and University of Toronto unlock clues to thyroid cancer

November 15, 2010

Iden­ti­fi­ca­tion of poten­tial bio­mark­er shows promise for the devel­op­ment of per­son­al­ized treat­ment

Toron­to, ON ― Novem­ber 15, 2010 ― Researchers at Mount Sinai Hos­pi­tal and the Uni­ver­si­ty of Toron­to have uti­lized pro­teom­ic tech­nolo­gies to dis­cov­er pro­teins secret­ed by thy­roid can­cer cell lines to iden­ti­fy and char­ac­ter­ize poten­tial bio­mark­ers for the future man­age­ment of thy­roid car­ci­no­mas.

The study recent­ly pub­lished in the Jour­nal of Pro­teome Research is of par­tic­u­lar impor­tance because these bio­mark­ers have the poten­tial to aid oncol­o­gists in deter­min­ing the aggres­sive­ness of the can­cer so appro­pri­ate treat­ment plans can be devel­oped for patients. Thy­roid can­cer rep­re­sents 90% of all endocrine malig­nan­cies with an esti­mat­ed annu­al inci­dence of 122,800 cas­es world­wide and approx­i­mate­ly 33,000 new­ly diag­nosed cas­es in North Amer­i­ca.

“We know that about 10 to 15 per cent of thy­roid can­cers are aggres­sive. Our hope is that out of this research a diag­nos­tic test can be devel­oped that will allow us to detect aggres­sive forms of the can­cer ear­ly so we cre­ate rig­or­ous treat­ment plans that will help improve out­comes for patients,” said endocri­nol­o­gist Dr. Paul Wal­fish, Alex and Simona Shnaider Research Chair in Thy­roid Oncol­o­gy at Mount Sinai Hos­pi­tal, Pro­fes­sor Emer­i­tus at the Uni­ver­si­ty of Toron­to, and the senior author of the study. “On the oth­er side of the equa­tion, if we deter­mine a patient’s can­cer is a non-aggres­sive form the treat­ment plan can be less inten­sive, mak­ing it eas­i­er for patients to tol­er­ate, and have a less­er impact on their qual­i­ty of life.”

Dr. Wal­fish and his team employed liq­uid chro­matog­ra­phy-mass spec­trom­e­try for iden­ti­fi­ca­tion of pro­teins secret­ed by aggres­sive and non-aggres­sive thy­roid can­cer cell lines. Among the major­i­ty of the 46 high con­fi­dence secre­to­ry pro­teins iden­ti­fied, 31 have not yet been report­ed in thy­roid can­cer demon­strat­ing the abil­i­ty of secre­tome analy­sis to iden­ti­fy poten­tial bio­mark­er can­di­dates for cor­re­la­tion with clin­i­cal man­age­ment of thy­roid can­cer.

“Six pro­teins secret­ed by thy­roid can­cer cells could be inde­pen­dent­ly ver­i­fied in cell lines, tumor xenografts in immuno­com­pro­mised mice, as well as tumor tis­sues and blood sam­ples of thy­roid can­cer patients,” said Dr. Ran­ju Ral­han, Co-Direc­tor of the Alex and Simona Shnaider Research Lab­o­ra­to­ry in Mol­e­c­u­lar Oncol­o­gy at Mount Sinai Hos­pi­tal. “This under­scores their poten­tial as can­di­date thy­roid can­cer bio­mark­ers. Clin­i­cal tri­als will still need to be under­tak­en to val­i­date our research, but we are very hope­ful that this will lead to a diag­nos­tic test.”

The stud­ies also revealed that it’s the nuclear and/or cyto­plas­mic local­iza­tion of these pro­teins in human thy­roid can­cer tis­sues that might have clin­i­cal rel­e­vance. Notably, sim­i­lar sub­cel­lu­lar local­iza­tion of these pro­teins could be observed in xenografts of thy­roid can­cer cells in NOD/SCID/gamma mice as well. Impor­tant­ly, pro­thy­mosin alpha (PTMA) was par­tic­u­lar­ly ele­vat­ed in aggres­sive anaplas­tic thy­roid car­ci­no­mas com­pared to the more dif­fer­en­ti­at­ed pap­il­lary thy­roid can­cer indi­cat­ing it may serve as a mark­er for aggres­sive car­ci­no­mas upon val­i­da­tion in a larg­er study.

“To our knowl­edge this study is the first report on the iden­ti­fi­ca­tion of bio­tinidase and nucle­olin in thy­roid can­cer,” added Dr. Wal­fish. “Fur­ther, in depth stud­ies showed a pro­tein called PTMA, a het­e­rochro­matin remod­el­ing pro­tein, is sig­nif­i­cant­ly ele­vat­ed in well dif­fer­en­ti­at­ed thy­roid car­ci­no­mas com­pared to ade­no­mas and non-tox­ic goitres.”

Large scale analy­sis of these pro­teins in sera of thy­roid can­cer patients and char­ac­ter­i­za­tion of their expres­sion in can­cer tis­sues may serve as the next step towards eval­u­at­ing their suit­abil­i­ty as can­di­date can­cer mark­ers. Thus, these researchers have suc­cess­ful­ly demon­strat­ed the appli­ca­tion of pro­teom­ic tech­nolo­gies for dis­cov­ery and ver­i­fi­ca­tion of pro­teins secret­ed by cul­tured thy­roid can­cer cells and large scale val­i­da­tion will pave the way for devel­op­ment of min­i­mal­ly inva­sive bio­mark­ers for future clin­i­cal appli­ca­tions in thy­roid can­cer as well as oth­er epithe­lial can­cers.

Dr. Wal­fish and his team includ­ing co-direc­tor Dr. Ran­ju Ral­han, Dr. Christi­na MacMil­lan and lab­o­ra­to­ry co-work­ers Lawrence Kashat, Antho­ny So and X. Meng of the Shnaider Lab­o­ra­to­ry of Mol­e­c­u­lar Oncol­o­gy in the Depart­ment of Pathol­o­gy and Lab­o­ra­to­ry Med­i­cine, in col­lab­o­ra­tion with Dr. K.W. Michael Siu’s team in the Depart­ment of Chem­istry and Cen­tre for Research and Mass Spec­trom­e­try at York Uni­ver­si­ty, and Dr. Lau­rie E. Ailles in the Ontario Can­cer Insti­tute, Uni­ver­si­ty Hos­pi­tal Net­work, devel­oped a strat­e­gy to iden­ti­fy thy­roid can­cer bio­mark­ers.

The research was made pos­si­ble by sup­port from the Mount Sinai Hos­pi­tal Foun­da­tion Da Vin­ci Fundrais­er, Alex and Simona Shnaider Chair in Thy­roid Oncol­o­gy, Tem­my Lat­ner Foun­da­tion and the Mount Sinai Hos­pi­tal Depart­ment of Med­i­cine Research Fund.

An abstract of the study enti­tled Secre­tome-Based Iden­ti­fi­ca­tion and Char­ac­ter­i­za­tion of Poten­tial Bio­mark­ers in Thy­roid Can­cer can be found online at


About Mount Sinai Hos­pi­tal
Mount Sinai Hos­pi­tal is an inter­na­tion­al­ly rec­og­nized, 472-bed acute care aca­d­e­m­ic health sci­ences cen­tre affil­i­at­ed with the Uni­ver­si­ty of Toron­to. It is known for excel­lence in the pro­vi­sion of com­pas­sion­ate patient care, inno­v­a­tive edu­ca­tion, and lead­ing-edge research. Mount Sinai’s Cen­tres of Excel­lence include Wom­en’s and Infants’ Health; Surgery and Oncol­o­gy; Acute and Chron­ic Med­i­cine; Lab­o­ra­to­ry Med­i­cine and Infec­tion Con­trol, and the Samuel Lunen­feld Research Insti­tute. For more infor­ma­tion about Mount Sinai Hos­pi­tal, please vis­it us online at

For more infor­ma­tion, please con­tact:

Rob McMa­hon
Mount Sinai Hos­pi­tal
Media and Com­mu­ni­ca­tions Spe­cial­ist
t: 416–586-4800 ext. 8306
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