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 ^99mTc- sestamibi (MIBI) and file heterogeneity of p-glycoproteln expression in tumor tissues. Methods: Twenty patients during initial presentation and 10 patients during post-therapy evaluation underwent contemporaneous ^99mTc-MIBI imaging and surgery or biopsy. Immunohistochemical studies were performed on multiple nonconsecutive sections of the same tumor using a p-glycoprotein- specific monoclonal antibody, JSB-1. Tumor-to-background (T/B) ratios were correlated with the level and heterogeneity of p-glycoprotein expression determined by immunohistochemical studies. Results: The T/B ratios were lower for those tumors with strong p-glycoprotein expression (Group 1) than those with strong-to-weak expression (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 groups (p < 0.005). Although T/B ratios for Group 1 and Group 3 were clearly distinct from one another with no overlapping values, the values for Group 2 overlapped with those of Group I and Group 3. When we evaluated the entire patient group with excluding those with strong-to-weak expression, although the p value remained the same (p < 0.001), we obtained a stronger correlation between T/B ratios and p-glycoprotein expression (r = 0.808 versus 0.735). Conclusion: Due to the heterogeneous expression of p-glycoprotein, both immunohistochemistry and ^99mTc-MIBI scintigraphy may yield confounding results by contrasting with one another if the presence or absence of p- glycoprotein is not extensively explored. Although our data confirmed that ^99mTc-MIBI imaging is useful in the determination of the presence of multidrug resistance in patients with breast cancer, the issue of heterogeneous expression of the antigen should be further investigated when unexpected results are obtained.