Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, 55905, USA.
Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, 55905, USA.
Hum Pathol. 2023 May;135:35-44. doi: 10.1016/j.humpath.2023.03.001. Epub 2023 Mar 9.
Intraluminal crystalloids are a common finding within malignant prostatic acini and are infrequently identified within benign glands. The proteomic composition of these crystalloids remains poorly understood and may provide insight regarding prostate cancer pathogenesis. Laser microdissection-assisted liquid chromatography-tandem mass spectrometry (LMD-LC-MS/MS) was performed to compare proteomic composition of corpora amylacea within benign acini (n = 9), prostatic adenocarcinoma-associated crystalloids (n = 8), benign (n = 8), and malignant prostatic acini (n = 6). The expression of candidate biomarkers was then measured in urine specimens from patients with (n = 8) and without prostate cancer (n = 10) using ELISA, and immunohistochemistry-based expression in adjacent prostate cancer and benign glands was assessed in 56 whole-slide sections from radical prostatectomy specimens. LMD-LC-MS/MS revealed enrichment for the C-terminal portion of growth and differentiation factor 15 (GDF15) in prostatic crystalloids. Although urinary GDF15 levels were higher in patients with prostatic adenocarcinoma compared to those without (median: 1561.2 versus 1101.3, arbitrary units), this did not meet statistical significance (P = 0.07). Immunohistochemistry for GDF15 revealed occasional positivity in benign glands (median H-score: 30, n = 56), and diffuse positivity in prostatic adenocarcinoma (median H-score: 200, n = 56, P < 0.0001). No significant difference was identified within different prognostic grade groups of prostatic adenocarcinoma, or within malignant glands with large cribriform morphology. Our results show that the C-terminal portion of GDF15 is enriched in prostate cancer-associated crystalloids, and higher GDF15 expression is seen in malignant rather than benign prostatic acini. Improved understanding of the proteomic composition of prostate cancer-associated crystalloids provides the rationale for evaluating GDF15 as a urine-based biomarker of prostate cancer.
腔内结晶体是恶性前列腺腺泡内的常见发现，在良性腺体中很少被发现。这些结晶体的蛋白质组组成仍知之甚少，可能为前列腺癌发病机制提供了一些见解。采用激光显微切割辅助液相色谱-串联质谱（LMD-LC-MS/MS）比较良性腺泡内的 corpora amylacea（n=9）、前列腺腺癌相关结晶体（n=8）、良性（n=8）和恶性前列腺腺泡（n=6）的蛋白质组组成。然后使用 ELISA 测量了来自患有（n=8）和不患有前列腺癌（n=10）的患者尿液标本中候选生物标志物的表达，并在 56 张前列腺癌根治术标本的全切片中评估了相邻前列腺癌和良性腺体的免疫组织化学表达。LMD-LC-MS/MS 显示前列腺结晶体中生长分化因子 15（GDF15）的 C 端部分富集。尽管前列腺腺癌患者的尿 GDF15 水平高于无前列腺癌患者（中位数：1561.2 与 1101.3，任意单位），但这没有统计学意义（P=0.07）。GDF15 的免疫组化显示良性腺体中偶尔出现阳性（中位数 H 评分：30，n=56），前列腺腺癌中弥漫性阳性（中位数 H 评分：200，n=56，P<0.0001）。在不同预后分级的前列腺腺癌组或在具有大筛状形态的恶性腺体中，未发现明显差异。我们的结果表明，GDF15 的 C 端部分在前列腺癌相关结晶体中富集，并且在恶性而不是良性前列腺腺泡中观察到更高的 GDF15 表达。对前列腺癌相关结晶体蛋白质组组成的深入了解为评估 GDF15 作为前列腺癌尿液生物标志物提供了依据。
