Cancel Mathilde, Castellier Claire, Debiais-Delpech Celine, Charles Thomas, Rozet François, Rioux-Leclercq Nathalie, Mathieu Romain, Beltjens Françoise, Cormier Luc, Bruyère Franck, Fromont Gaëlle
Inserm UMR1069 "Nutrition, Croissance et Cancer" Université de Tours, CHRU Bretonneau, Tours, France; Department of Oncology, Tours, France.
Department of Pathology, Tours, France.
Urol Oncol. 2021 Jan;39(1):74.e17-74.e23. doi: 10.1016/j.urolonc.2020.07.007. Epub 2020 Jul 30.
To determine whether small cell neuroendocrine prostate cancers (NEPCa) emerging after anti-androgen treatments are different from the rarest cases diagnosed de novo, and to identify effective predictive markers.
The expression of neuroendocrine markers, androgen receptor (AR) and androgen-regulated genes, as well as markers of aggressiveness, were analyzed by immunohistochemistry on a tissue microarray containing samples of 30 sNEPCa, either pure or admixed with conventional PCa, and including 14 cases diagnosed de novo and 16 cases subsequent to prior androgen deprivation.
Chromogranin A is a better marker of NE differentiation than synaptophysin in post-treatment NEPCa, with 94% and 44% of positive tumors, respectively, while both markers are equally expressed in de novo cases. Despite the acquisition of a NE phenotype, more than half of NEPCa expressed AR and the androgen-regulated gene NKX3.1, more frequently in cases admixed with conventional PCa. TTF1 staining, present in half of NEPCa, was associated with loss of androgen-regulated genes and with markers of aggressiveness, including increased proliferation, Zeb1 expression and PTEN loss. In multivariate analysis, only TTF1 expression was significantly associated with shorter overall survival.
These results suggest the persistence of androgen signaling in a number of NEPCa cases, and the interest of TTF1 staining as a predictive biomarker.
确定抗雄激素治疗后出现的小细胞神经内分泌前列腺癌（NEPCa）是否与罕见的原发性诊断病例不同，并识别有效的预测标志物。
通过免疫组织化学分析神经内分泌标志物、雄激素受体（AR）和雄激素调节基因的表达，以及侵袭性标志物，所用组织芯片包含30例sNEPCa样本，包括单纯型或与传统前列腺癌混合型，其中14例为原发性诊断病例，16例为既往雄激素剥夺治疗后的病例。
在治疗后的NEPCa中，嗜铬粒蛋白A比突触素是更好的NE分化标志物，阳性肿瘤分别为94%和44%，而在原发性病例中这两种标志物表达相当。尽管获得了NE表型，但超过一半的NEPCa表达AR和雄激素调节基因NKX3.1，在与传统前列腺癌混合的病例中更常见。TTF1染色见于一半的NEPCa，与雄激素调节基因的缺失以及侵袭性标志物相关，包括增殖增加、Zeb1表达和PTEN缺失。多因素分析中，只有TTF1表达与较短的总生存期显著相关。
这些结果提示在一些NEPCa病例中雄激素信号持续存在，以及TTF1染色作为预测生物标志物的意义。
