Biomarkers of parathyroid carcinoma

Abstract

The diagnosis of parathyroid carcinoma can be challenging adjuvant therapies such as radiotherapy chemotherapy are not particularly beneficial in the management of this disease creating a challenge when dealing with unresectable recurrent metastatic malignancy. We investigated the expression profile of biomarkers that represent potential markers of malignancy or targets for novel therapies in this disease. We constructed a tissue microarray of parathyroid carcinomas from 10 patients as well as parathyroid adenomas from 25 patients stained the slides for 34 proteins involved in angiogenesis (plateletderived growth factor receptor (PDGFR)-α PDGFR-β vascular endothelial growth factor receptor-2 (VEGFR-2) epidermal growth factor receptor (EGFR)) inflammation (cyclooxygenase (COX)-1 COX-2) cell adhesion (matrix metalloproteinase (MMP)-1 CD9 keratin 7) cell cycle (Cdc2p34 cyclin D1 retinoblastoma (Rb) p27 p21 parafibromin Bmi-1 14-3-3σ p53) apoptosis (Bcl-2a Mcl-1 Bcl-xL glutathione-S-transferase-isoenzyme π (Gst-π)) along with some markers of the sonic hedgehog (Smo SHH Gli-1 Gli-2 Gli-3 patched) mTOR (AKT mammalian target of rapamycin (mTOR) Forkhead box O (FoxO)-1) WNT (Wisp-1 Wisp- 2 β-catenin) signal transduction pathways. Protein expression was determined using computerized image analysis software (Spectrum Plus© Aperio). Bcl-2a parafibromin Rb p27 were significantly decreased to variable degrees in all parathyroid carcinomas. COX-12 CD9 MMP-1 FoxO-1 VEGFR-2 PDGFR-αβ Gst-π Gli-1 Gli-2 Gli-3 patched were expressed in the majority of benign malignant tumor cells. These results indicate that the use of a panel that includes Bcl-2a parafibromin Rb p27 may be helpful in the assessment of atypical parathyroid neoplasms. Although the majority of other markers studied are also expressed in both benign malignant parathyroid neoplasms we have identified several potentially important target proteins related to angiogenesis cell proliferation along with COX-12 Gst-π members of sonic hedgehog pathway that may be therapeutic targets in parathyroid carcinoma. While these results are preliminary a Successful Outcome Of A Clinical Trial Directed Against These Novel Targets Would Provide Much Needed Systemic Adjuvant Treatment For Patients With Metastatic Parathyroid Carcinoma. © 2012 Springer Science+Business Media LLC.