P-gp and MRP1 Expression in Parathyroid Tumors Related to Histology, Weight and 99mTc-Sestamibi Imaging Results

Objective: P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP) are membrane efflux pumps that may have a role in the kinetics of Tc-99m-sestamibi (MIBI) in parathyroid tumors. P-gp and MRP1 expression in parathyroid tumors was studied and related to histology, weight and pre- and intraoperative MIBI imaging results. Design: Patient cohort study Setting: Tertiary referral center Patients: Thirty-three patients underwent radioguided parathyroidectomy for primary or secondary hyperparathyroidism. Main outcome measures: P-gp and MRP1 expression. Methods: Dual-phase Tc-99m-MIBI scintigraphy and SPECT results were compared to the surgical findings. Radioactivity and weight of resected parathyroid tumors were measured. Intraoperative radioactivity measurements were decay corrected. After routine histology immunohistochemistry was performed using C494 monoclonal antibodies to P-gp and MRP1r1 to MRP1. P-gp and MRP1 expression were scored covering both distribution of positivity and degree of immunostaining semi quantitatively. Results: P-gp and MRP1 staining was observed in 97% and 43% of the glands respectively. P-gp staining was positive in 91% (21/23) of the adenomas and in all 36 hyperplastic glands. MRP1 staining was positive in 22% (5/23) of the adenomas and in 61% (22/36) of the hyperplastic glands. P-gp or MRP1 expression did not correlate with preoperative Tc-99m-MIBI imaging or intraoperative radioactivity. Parathyroid weight was associated with preoperative MIBI imaging results and MIBI uptake measured during surgery. Conclusion: P-gp and MRP1 expression did not correlate with Tc-99m-MIBI uptake in parathyroid tumors. Parathyroid weight remains the major known factor influencing Tc-99m-MIBI uptake.