PMID- 21468754 OWN - NLM STAT- MEDLINE DCOM- 20111121 LR - 20211203 IS - 1776-260X (Electronic) IS - 1776-2596 (Linking) VI - 6 IP - 2 DP - 2011 Jun TI - Mammalian target of rapamycin expression in poorly differentiated endocrine carcinoma: clinical and therapeutic future challenges. PG - 65-8 LID - 10.1007/s11523-011-0171-z [doi] AB - 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. FAU - Catena, Laura AU - Catena L AD - Istituto di Oncologia, Policlinico di Monza, Via C. Amati, Monza, MB, Italy. laura.catena@policlinicodimonza.it FAU - Bajetta, Emilio AU - Bajetta E FAU - Milione, Massimo AU - Milione M FAU - Ducceschi, Monika AU - Ducceschi M FAU - Valente, Monica AU - Valente M FAU - Dominoni, Francesca AU - Dominoni F FAU - Colonna, Valentina AU - Colonna V LA - eng PT - Journal Article DEP - 20110406 PL - France TA - Target Oncol JT - Targeted oncology JID - 101270595 RN - 0 (Protein Kinase Inhibitors) RN - 9HW64Q8G6G (Everolimus) RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - W36ZG6FT64 (Sirolimus) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Animals MH - Cell Line, Tumor MH - Everolimus MH - Female MH - Humans MH - Male MH - Mice MH - Middle Aged MH - Molecular Targeted Therapy/methods MH - Neuroendocrine Tumors/drug therapy/*metabolism MH - Prognosis MH - Protein Kinase Inhibitors/therapeutic use MH - Signal Transduction MH - Sirolimus/analogs & derivatives/therapeutic use MH - TOR Serine-Threonine Kinases/*biosynthesis MH - Young Adult EDAT- 2011/04/07 06:00 MHDA- 2011/12/13 00:00 CRDT- 2011/04/07 06:00 PHST- 2010/11/19 00:00 [received] PHST- 2011/03/09 00:00 [accepted] PHST- 2011/04/07 06:00 [entrez] PHST- 2011/04/07 06:00 [pubmed] PHST- 2011/12/13 00:00 [medline] AID - 10.1007/s11523-011-0171-z [doi] PST - ppublish SO - Target Oncol. 2011 Jun;6(2):65-8. doi: 10.1007/s11523-011-0171-z. Epub 2011 Apr 6.