Mammalian target of rapamycin (mTOR) expression analysis and therapeutic approach in lung and gastroenteropancreatic poorly differentiated endocrine carcinoma (PDEC)

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Introduction: PDEC clinically include gastroenteropancreatic PDEC, small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC). These tumors are clinically similar and aggressive and they are usually treated with platinum compounds. mTOR signalling pathway has emerged as a promising target for well-differentiated endocrine carcinoma therapy. Because of varying behavior, PDEC are usually excluded from clinical trials employing the mTOR inhibitor RAD001.

Aim(s): We conducted a retrospective analyses of incidence of PDEC in a mono-istitutional series revised with WHO/Travis classification and validated with immunohistochemestry (IHC) for general and specific endocrine markers. We also aimed at testing if mTOR as expressed in the human PDEC.

Materials and methods: Between 1984 and 2007, 640 NETs referred to our Institution, of whom (7.5%) were diagnosed as PDEC. The staining for mTOR was optimized employing slides of normal kidney as positive control. To ensure antibody specificity, consecutive sections were incubated in the absence of a primary antibody. In such cases, no immunostaining was detected. The immunoreactivity was evaluated on a semiquantitative scale considering the extent (score: 0-4) and the intensity (score: 0-3) of staining. The product was used to obtain an immunostaining score (total score 0-12).

Conference: 7th Annual ENETSConcerence (2010)

Presenting Author:

Authors: Catena L, Milione M, Pusceddu S, Ducceschi M, Avarino M,

Keywords: poorly differentiated endocrine carcinoma, mTOR, RAD001,