Kostakoglu L, Ruacan S, Ergün E L, Sayek I, Elahi N, Bekdik C F
Department of Nuclear Medicine, Hacettepe University Medical Faculty, Ankara, Turkey.
J Nucl Med. 1998 Jun;39(6):1021-6.
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 the heterogeneity of p-glycoprotein expression in tumor tissues.
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.
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 1 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).
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.
我们前瞻性地研究了总共30例乳腺癌患者,以评估99mTc-司他米比(MIBI)的积聚程度与肿瘤组织中P-糖蛋白表达异质性之间的关系。
20例初诊患者和10例治疗后评估患者同期接受了99mTc-MIBI成像及手术或活检。使用P-糖蛋白特异性单克隆抗体JSB-1对同一肿瘤的多个非连续切片进行免疫组织化学研究。肿瘤与本底(T/B)比值与免疫组织化学研究确定的P-糖蛋白表达水平及异质性相关。
P-糖蛋白强表达的肿瘤(第1组)的T/B比值低于强至弱表达的肿瘤(第2组)或弱至无表达的肿瘤(第3组)(分别为1.32±0.19、1.85±0.56和2.86±1.06)。3组之间的T/B比值存在统计学显著差异(p<0.005)。虽然第1组和第3组的T/B比值明显不同,无重叠值,但第2组的值与第1组和第3组的值重叠。当我们排除强至弱表达的患者评估整个患者组时,虽然p值保持不变(p<0.001),但我们获得了T/B比值与P-糖蛋白表达之间更强的相关性(r=0.808对0.735)。
由于P-糖蛋白的异质性表达,如果不广泛探究P-糖蛋白的存在与否,免疫组织化学和99mTc-MIBI闪烁扫描可能会因相互对比而产生混淆结果。虽然我们的数据证实99mTc-MIBI成像有助于确定乳腺癌患者多药耐药的存在,但当获得意外结果时,抗原异质性表达问题应进一步研究。