Vinceneux Armelle, Bruyère Franck, Haillot Olivier, Charles Thomas, de la Taille Alexandre, Salomon Laurent, Allory Yves, Ouzaid Idir, Choudat Laurence, Rouprêt Morgan, Comperat Eva, Houede Nadine, Beauval Jean-Baptiste, Vourc'h Patrick, Fromont Gaëlle
Department of Pathology, CHU de tours, Université François Rabelais, Tours, France.
INSERM UMR 1069, Tours, France.
Prostate. 2017 Sep;77(12):1242-1250. doi: 10.1002/pros.23383. Epub 2017 Jul 12.
Ductal adenocarcinoma (DAC) is a rare and aggressive subtype of prostate cancer (PCa). In the present study, we analyzed the clinical and biological characteristics of DAC, in comparison with high grade conventional acinar PCa.
Samples and data were retrospectively collected from seven institutions and centrally reviewed. Immunohistochemistry was performed on tissue microarrays to assess the expression of candidate proteins, based on the molecular classification of PCa, including ERG, PTEN, and SPINK1. SPOP mutations were investigated from tumor DNA by Sanger sequencing. Relationships with outcome were analyzed using log-rank analysis and multivariable Cox regression.
Among 56 reviewed prostatectomy specimens, 45 cases of DAC were finally confirmed. The pathological stage was pT3 in more than 66% of cases. ERG was expressed in 42% of DAC, SPINK1 in 9% (all ERG-negative), and two cases (ERG-negative) harbored a SPOP mutation. Compared to high grade conventional PCa matched for the pathological stage, cell proliferation was higher (P = 0.04) in DAC, and complete PTEN loss more frequent (P = 0.023). In multivariate analysis, SPINK1 overexpression (P = 0.017) and loss of PSA immunostaining (P = 0.02) were significantly associated with biochemical recurrence.
these results suggest that, despite biological differences that highlighted DAC aggressiveness, the molecular classification recently proposed in conventional PCa could also be applied in DAC.
导管腺癌(DAC)是前列腺癌(PCa)中一种罕见且侵袭性强的亚型。在本研究中,我们分析了DAC的临床和生物学特征,并与高级别传统腺泡状PCa进行比较。
回顾性收集了七个机构的样本和数据,并进行集中审查。基于PCa的分子分类,包括ERG、PTEN和SPINK1,对组织芯片进行免疫组织化学检测,以评估候选蛋白的表达。通过Sanger测序从肿瘤DNA中检测SPOP突变。使用对数秩分析和多变量Cox回归分析与预后的关系。
在56份经审查的前列腺切除标本中,最终确诊45例DAC。超过66%的病例病理分期为pT3。42%的DAC表达ERG,9%表达SPINK1(均为ERG阴性),2例(ERG阴性)存在SPOP突变。与病理分期匹配的高级别传统PCa相比,DAC的细胞增殖更高(P = 0.04),PTEN完全缺失更常见(P = 0.023)。多变量分析中,SPINK1过表达(P = 0.017)和PSA免疫染色缺失(P = 0.02)与生化复发显著相关。
这些结果表明,尽管生物学差异凸显了DAC的侵袭性,但最近在传统PCa中提出的分子分类也可应用于DAC。