INFLUENCE OF THE HETEROGENEITY OF P-GLYCOPROTEIN EXPRESSION ON TECHNETIUM-99M-MIBI UPTAKE IN BREAST-CANCER

We prospectively studied a total of 30 patients with breast cancer to evaluate the relationship between the degree of accumulation of (99m)- sestamibi (MIBI) and the heterogeneity of p-glycoprotein expression in tumor tissues. Methods: Twenty patients during initial presentation a nd 10 patients during post-therapy evaluation underwent contemporaneou s Tc-99m-MIBI imaging and surgery or biopsy. Immunohistochemical studi es were performed on multiple nonconsecutive sections of the same tumo r using a p-glycoprotein-specific monoclonal antibody, JSB-1. Tumor-to -background (T/B) ratios were correlated with the level and heterogene ity of p-glycoprotein expression determined by immunohistochemical stu dies. Results: The T/B ratios were lower for those tumors with strong p-glycoprotein expression (Group 1) than those with strong-to-weak exp ression (Group 2) or those with weak-to-no expression (Group 3) (1.32 +/- 0.19 and 1.85 +/- 0.56 and 2.86 +/- 1.06, respectively). There was statistically significant difference in T/B ratios between all 3 grou ps (p < 0.005). Although T/B ratios for Group 1 and Group 3 were clear ly distinct from one another with no overlapping values, the values fo r Group 2 overlapped with those of Group I and Group 3. When we evalua ted the entire patient group with excluding those with strong-to-weak expression, although the p value remained the same (p < 0.001), we obt ained a stronger correlation between T/B ratios and p-glycoprotein exp ression (r = 0.808 versus 0.735). Conclusion: Due to the heterogeneous expression of p-glycoprotein, both immunohistochemistry and Tc-99m-MI BI scintigraphy may yield confounding results by contrasting with one another if the presence or absence of p-glycoprotein is not extensivel y explored. Although our data confirmed that Tc-99m-MIBI imaging is us eful in the determination of the presence of multidrug resistance in p atients with breast cancer, the issue of heterogeneous expression of t he antigen should be further investigated when unexpected results are obtained.