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Immunohistochemical Validation of PSMA Expression Measured by 68Ga-PSMA PET/CT in Primary Prostate Cancer
The Journal of Nuclear Medicine ( IF 9.3 ) Pub Date : 2018-02-01 , DOI: 10.2967/jnumed.117.195172
Nadine Woythal 1 , Ruza Arsenic 2 , Carsten Kempkensteffen 3 , Kurt Miller 4 , Jan-Carlo Janssen 5 , Kai Huang 1 , Marcus R Makowski 5 , Winfried Brenner 1 , Vikas Prasad 6
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68Ga-labeled prostate-specific membrane antigen (68Ga-PSMA) PET/CT has a proven role in staging and restaging of prostate cancer (PCA). The aims of this study were to evaluate the association of intraprostatic 68Ga-PSMA PET/CT findings and PSMA expression in immunohistochemical staining and generate a cutoff value for differentiation between normal prostate (PN) and PCA. Methods: The data of 31 patients (mean age, 67.2 y) who underwent prostatectomy and preoperative PET were retrospectively analyzed. On PET, focally increased uptake in the prostate was suggestive of tumor. A region of interest was placed on the suggestive area to generate an SUVmax; a similar region of interest was placed on adjacent visually PN. Both PCA and PN were stained with monoclonal anti-PSMA antibody (clone 3E6, 1:100, M3620). Results: All intraprostatic PCA lesions on PET could be confirmed histopathologically. In PN sections (n = 31), median staining intensity was mild, median percentage of stained cells was 20% ± 14.24%, and median immunoreactive score (IRS) was 1. In PCA sections (n = 31), median IRS was 3, median staining intensity was strong, and median percentage of stained cells was 80% ± 16.46%. The mean SUVmax (±SD) of PCA (14.06 ± 15.56) was significantly higher than that of PN (2.43 ± 0.63; P < 0.001). Receiver-operating-characteristic curve analyses of the SUVmax of PCA, validated by immunohistochemical staining in 62 tissue samples, showed the best cutoff to be 3.15 (sensitivity, 97%; specificity, 90%; area under curve, 0.987). Applied to multifocal PCA, it resulted in sensitivity and specificity of 87% and 97% respectively. The mean SUVmax of PCA and PN for an IRS of less than 2 (n = 26; 2.52 ± 0.64) was significantly lower than the mean SUVmax for an IRS of 2 or more (n = 36; 12.38 ± 15.02; P < 0.001). The mean SUVmax was significantly lower in PCA samples with fewer than 50% stained cells (n = 30; 2.81 ± 2.35) than in samples with 50% or more (n = 32; 13.34 ± 15.55; P < 0.001). There was no correlation between the SUVmax of PCA and Gleason score (P = 0.54). Conclusion: This study showed that SUVmax on 68Ga-PSMA PET/CT correlates significantly with PSMA expression in primary PCA, enabling the detection of PCA with a high sensitivity and specificity.



中文翻译:

68 Ga-PSMA PET / CT对原发性前列腺癌中PSMA表达的免疫组织化学验证

68 Ga标记的前列腺特异性膜抗原(68 Ga-PSMA)PET / CT在前列腺癌(PCA)的分期和再分期中具有公认的作用。这项研究的目的是评估免疫组织化学染色中前列腺内68 Ga-PSMA PET / CT结果与PSMA表达之间的关联,并为正常前列腺(PN)和PCA之间的分化产生一个临界值。方法:回顾性分析31例(平均年龄67.2岁)行前列腺切除术和术前PET检查的患者的资料。在PET上,前列腺摄取的局灶性增加提示肿瘤。将感兴趣的区域放置在提示区域上以生成SUV max; 将相似的感兴趣区域放置在相邻的视觉PN上。PCA和PN均用单克隆抗PSMA抗体(克隆3E6,1:100,M3620)染色。结果: PET上所有前列腺内PCA病变均可通过组织病理学确认。在PN切片(n = 31)中,中度染色强度中等,染色细胞的中值百分比为20%±14.24%,中值免疫反应评分(IRS)为1。在PCA切片中(n = 31),中值IRS为3。 ,中值染色强度很强,染色细胞的中值百分比为80%±16.46%。PCA(14.06±15.56)的平均SUV max(±SD)显着高于PN(2.43±0.63; P <0.001)。SUV的接收器操作特性曲线分析通过免疫组织化学染色在62个组织样本中验证的最大PCA值的最佳截止值为3.15(灵敏度为97%;特异性为90%;曲线下面积为0.987)。应用于多焦点PCA,其敏感性和特异性分别为87%和97%。IRS小于2时PCA和PN的平均SUV maxn = 26; 2.52±0.64)显着低于IRS为2或更高时的平均SUV maxn = 36; 12.38±15.02; P < 0.001)。染色细胞少于50%的PCA样品(n = 30; 2.81±2.35)的平均SUV max显着低于50%或更高的PCA样品(n = 32; 13.34±15.55; n = 32。P <0.001)。SUV max的PCA与Gleason评分之间无相关性(P = 0.54)。结论:这项研究表明,在68 Ga-PSMA PET / CT上的SUV max与原发性PCA中的PSMA表达显着相关,从而能够以高灵敏度和特异性检测PCA。

更新日期:2018-02-01
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