title: Mammalian target of rapamycin expression in poorly differentiated endocrine carcinoma: clinical and therapeutic future challenges.
abstract: While the mammalian target of rapamycin (mTOR) signaling pathway is a promising target for well-differentiated endocrine carcinoma therapy with the mTOR inhibitor everolimus (RAD001), poorly differentiated endocrine carcinomas (PDECs) are usually excluded from clinical trials due to their aggressiveness. So far, mTOR activity in PDECs has only been tested in cell lines. This study reviewed 36 mono-institutional PDECs to determine mTOR expression. Slides of normal kidney as positive control were used to optimize mTOR staining. To ensure antibody specificity, consecutive sections were incubated in the absence of primary antibody. Immunoreactivity was evaluated on a semi-quantitative scale scoring the extent and intensity of staining. The product of these two scores was used to obtain a total immunostaining score. The main primary site of disease was the pancreas, and 83% of patients had stage IV disease. In 80% of samples, mTOR expression was maintained at similar levels, with no relationship to tumor origin or proliferation rate determined by MIB-1. This study seems to demonstrate that mTOR is expressed in human PDECs regardless of tumor site. Its role in relation to the activity of everolimus in this subset of patients needs to be confirmed.
authors.affiliation: Istituto di Oncologia, Policlinico di Monza, Via C. Amati, Monza, MB, Italy. laura.catena@policlinicodimonza.it
authors.forename: Laura
authors.initials: L
authors.lastname: Catena
authors.forename: Emilio
authors.initials: E
authors.lastname: Bajetta
authors.forename: Massimo
authors.initials: M
authors.lastname: Milione
authors.forename: Monika
authors.initials: M
authors.lastname: Ducceschi
authors.forename: Monica
authors.initials: M
authors.lastname: Valente
authors.forename: Francesca
authors.initials: F
authors.lastname: Dominoni
authors.forename: Valentina
authors.initials: V
authors.lastname: Colonna
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D045744:Cell Line, Tumor; D000068338:Everolimus; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000379:methods; D018358:Neuroendocrine Tumors / Q000188:drug therapy / Q000378:metabolism*; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D015398:Signal Transduction; D020123:Sirolimus / Q000031:analogs & derivatives / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000096:biosynthesis*; D055815:Young Adult
chemical_list: D047428:Protein Kinase Inhibitors; D000068338:Everolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus