背景:导管腺癌(DAC)和前列腺导管内癌(IDC-P)对所有目前可用的常规疗法反应较差。鉴于它们准确有效地消除了癌细胞,抗体-药物偶联物(ADC)已成为最有前途的抗癌治疗方法之一。然而,到目前为止,尚无ADC被批准用于前列腺癌(PCa)治疗。这项研究调查了DAC/IDC-P样品中TROP-2,HER2和CD46的表达,间接分析其作为治疗靶点的初步可行性,为今后两种情况的治疗提供依据。
方法:我们在2017年8月至2022年8月期间进行了一项回顾性研究,纳入了184名参与者(87名DAC/IDC-P患者和97名Gleason评分≥8的前列腺腺泡腺癌(PAC)患者),未接受过治疗。免疫组化染色检测DAC/IDC-P中TROP-2、HER2和CD46蛋白的差异表达,PAC,和正常的前列腺组织.
结果:与纯PAC组织相比,TROP-2在DAC/IDC-P和DAC/IDC-P相邻PAC组织中的表达显着升高(H评分68.8vs.43.8,p<0.001,59.8vs.43.8,p=0.022)。在不同的癌组织中没有观察到HER2表达的显著差异。与DAC/IDC-P相邻PAC和纯PAC组织相比,CD46在DAC/IDC-P组织中的表达显着升高(42.3vs.28.6,p=0.041,和42.3vs.分别为24.3,p=0.0035)。
结论:此处,DAC/IDC-P组织中TROP-2和CD46的表达高于纯PAC和正常前列腺组织。这一发现意味着靶向这两种蛋白质的ADC作为DAC/IDC-P的潜在未来治疗方法具有重要的前景。
BACKGROUND: Ductal Adenocarcinoma (DAC) and Intraductal Carcinoma of the Prostate (IDC-P) respond poorly to all the currently available conventional therapies. Given their accurate and efficient elimination of cancer cells, Antibody-Drug Conjugates (ADCs) have become one of the most promising anticancer treatments. However, no ADCs have so far been approved for Prostate Cancer (PCa) treatment. This study investigated TROP-2, HER2, and CD46 expression in DAC/IDC-P samples, indirectly analyzing their preliminary feasibility as therapeutic targets for future treatment of the two conditions.
METHODS: We conducted a retrospective study involving 184 participants (87 DAC/IDC-P patients and 97 Prostatic Acinar Adenocarcinoma (PAC) patients with a Gleason score ≥ 8) without prior treatment between August 2017 and August 2022. Immunohistochemical staining was employed to detect the differential protein expressions of TROP-2, HER2, and CD46 in DAC/IDC-P, PAC, and normal prostate tissues.
RESULTS: Compared to pure PAC tissues, TROP-2 expression was significantly higher in DAC/IDC-P and DAC/IDC-P-adjacent PAC tissues (H-score 68.8 vs. 43.8, p < 0.001, and 59.8 vs. 43.8, p = 0.022, respectively). No significant differences in HER2 expression were observed across different cancer tissues. Compared to both DAC/IDC-P-adjacent PAC and pure PAC tissues, CD46 expression was significantly higher in DAC/IDC-P tissues (42.3 vs. 28.6, p = 0.041, and 42.3 vs. 24.3, p = 0.0035, respectively).
CONCLUSIONS: Herein, TROP-2 and CD46 expression was higher in DAC/IDC-P tissues than in pure PAC and normal prostate tissues. This finding implies that ADCs targeting the two proteins hold significant promise as potential future treatments for DAC/IDC-P.