Activation of the Mammalian Target of Rapamycin (mTOR) Pathway in Thyroid Carcinomas
CT Elkins, M Leon, WL Frankel, OH Iwenofu. The Ohio State University Medical Center, Columbus, OH
Background: Emerging data suggests that alterations of the PI3K/AKT/mTOR pathway play an important, previously unrecognized role in thyroid carcinogenesis. mTOR represents a key mitogenic output of the PI3K activation cascade and is a potential therapeutic target. Several mTOR inhibitors are in clinical trials for various solid organ tumors. Thus, we hypothesized that demonstration of this pathway using immunohistochemistry might be predictive of potential benefit from mTOR inhibitors.
Design: A tissue microarray (TMA) was built from 86 thyroid carcinomas including: papillary thyroid carcinoma (PTC, n=36), follicular carcinoma (FC, n=13), medullary thyroid carcinoma (MTC, n=21), poorly differentiated thyroid carcinoma (PDC, n=5) and anaplastic carcinoma (AC, n=11). Sections were stained with antibodies to PI3K, p-AKT, p-mTOR, p70S6K and pS6 ribosomal protein (p-S6rp). Controls stained appropriately, and slides were reviewed by two pathologists. Staining of 5% of tumor cells was interpreted as positive.
Results: There is a high level of expression of PI3k, p-mTOR, p70S6k and p-S6rp in all histologic types of thyroid carcinoma (see Table 1). Of note, the p-AKT expression was very low across the different types of thyroid carcinoma, probably representing an AKT-independent mTOR pathway activation.
|PTC (% Pos)||FC (% Pos)||MTC (% Pos)||PDC (% Pos)||AC (% Pos)|
Conclusions: Our results indicate activation of the PI3K/mTOR/p70S6K/S6p pathway in all histologic types of thyroid carcinoma. This suggests a potential benefit from mTOR inhibitor in patients with thyroid carcinoma, especially in those with advanced disease. Prospective clinical trials are warranted to ascertain clinical utility.
Category: Head & Neck
Monday, March 9, 2009 1:00 PM
Poster Session II # 184, Monday Afternoon