The Relationship Between Scintimammography Of Breast Cancer And The Expression Of P-glycoprotein And Glutathione-S-transferase-π

Resistance to chemotherapeutic drugs continues to be one of the major unsolved problems in the treatment of breast cancer. Tc-99m-sestamibi (MIBI) scintimammography has provided exciting results in the diagnosis of breast cancer and recently evidence shown that Tc-99m-MIBI is a suitable transport substrate for P-glycoprotein. A potential advantage of Tc-99m-MIBI SPECT is its superiority to diagnose noninvasively the presence of P-glycoprotein overexpression in vivo,but it is not known whether it is a substrate for the glutathione-S-transferase TT (GST- TT ).Objective: The aim of the study is to evaluated the relationship of Tc-99m-SESTAMIBI (MIBI) uptake and washout inuntreated breast cancer patients between immunohistochemically analyses of glutathione-S-transferase n (GST- TT ) and P-glycoprotein (P-gp) expression. Methods:Thirty-six patients with untreated breast cancer were studied prospectively a week before their surgical operations. They were all injected intravenously with 740 MBq (20 mCi) Tc-99m-MIBI in the arm contralateral to the lesion. Planar images, with a matrix size of 256 x 256 pixels were then acquired . Anterior planar images were acquired at 10 and 180 minutes after the intravenous injection and the tumor-to-normal breast ratio (T:N) and washout index(WI) (early T:N-late T:N divided by early T:N) were calculated.Immunohistochemical analyses of P-glycoprotein and GST- TT expression were used to evaluate the removed tumor tissues after their surgical operations.Results: l.The early T:N ratios were significantly lower in 9patients with negative P-gp expression when compared with 27 patients with positive P-gp expression (main scores are 21.89,8.33 and Z=-3.32 p =0.002 two sides ). The washout index was significantly different among the two groups (f=3.59, p =0.001).2.On the other hand there is no significant relationship between negative and positive GST- n expression when calculated the early T:N ratio and WI. S.Though the expression of P-gp and GST- TC was different (75.00%,77.78%).4.There is a highco-expression rate of P-gp and GST- n (66.7%), and a strong correlation was found between the two markers in these untreated breast cancer patients. Conclusions: The co-expression of P-gp and GST- n is one of the major characteristics of untreated breast cancer, and Significant relationship was found between the two markers. Tc-99m-MIBI seems to be a good candidate for a noninvasive marker to diagnose MDR1 related to P-gp expression in breast cancer. Tc-99m-MIBI perhaps is not a substrate for the GST- TT . Double-phase scintimammography and washout index of Tc-99m -MIBI can be used as a simple functional test for in vivo imaging of tumoral P-gp expression in patients with untreated breast cancer.