Identification of New Target Proteins in Parathyroid Carcinomas
Ozgur Mete, Boban Erovic, Jonathan Irish, Sylvia L Asa. University Health Network, Toronto, ON, Canada
Background: Adjuvant therapies such as radiotherapy and chemotherapy are not particularly beneficial in the management of parathyroid carcinoma. This creates a challenge when dealing with unresectable recurrent and metastatic disease. Therefore, there is need for effective systemic adjuvant therapy in the management of recurrent or metastatic parathyroid carcinoma. We examined the expression profile of markers that are potential targets for novel therapies in this disease.
Design: We constructed a tissue microarray of parathyroid carcinomas from 10 patients and stained the slides for 32 proteins involved in angiogenesis (PDGFR-α, PDGFR-β, VEGFR2), inflammation (COX-1, COX-2), cell adhesion (MMP-1, CD9, keratin 7), cell cycle (Cdc2p34, cyclin D1, Rb, p27, p21, parafibromin, Bmi-1, 14-3-3σ) and apoptosis (Bcl-2a, Mcl-1, Bcl-Xl, p53) with along some markers of the sonic hedgehog (Smo, Shh, Gli-1, Gli-2, Gli-3, Patch), AKT/mTOR (FOXO-1, AKT, mTOR) and WNT (Wisp-1, Wisp-2, β-catenin) signal transduction pathways. Protein expression was determined using computerized image analysis software (Spectrum Plus©, Aperio).
Results: COX-1, CD9, MMP-1, FOXO-1, VEGFR2, PDGFR-α, PDGFR-β, Gli-1, Gli-2, Gli-3 and patched are diffusely expressed in parathyroid carcinoma. Parafibromin was lost in 90% of cases, along with loss of Rb and p27 in the same tumors.
Conclusions: We have demonstrated for the first time that sonic hedgehog pathway proteins as well as COX-1 are diffusely expressed in parathyroid carcinoma. In addition, markers related to angiogenesis and cell proliferation are also significantly expressed. Our preliminary data suggest that these markers may be targets for novel adjuvant therapies in the treatment of parathyroid carcinoma.
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 39, Tuesday Afternoon