PSP94表达缺失与前列腺特异性抗原（PSA）早期复发相关，并使缺失型前列腺癌的预后恶化。

Loss of PSP94 expression is associated with early PSA recurrence and deteriorates outcome of deleted prostate cancers.

作者信息

Luebke Andreas M, Attarchi-Tehrani Ali, Meiners Jan, Hube-Magg Claudia, Lang Dagmar S, Kluth Martina, Tsourlakis Maria Christina, Minner Sarah, Simon Ronald, Sauter Guido, Büscheck Franziska, Jacobsen Frank, Hinsch Andrea, Steurer Stefan, Schlomm Thorsten, Huland Hartwig, Graefen Markus, Haese Alexander, Heinzer Hans, Clauditz Till S, Burandt Eike, Wilczak Waldemar, Höflmayer Doris

机构信息

Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany.

General, Visceral and Thoracic Surgery Department and Clinic, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany.

出版信息

Cancer Biol Med. 2019 May;16(2):319-330. doi: 10.20892/j.issn.2095-3941.2018.0384.

DOI:10.20892/j.issn.2095-3941.2018.0384

PMID:31516752

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6713635/

Abstract

OBJECTIVE

Prostate secretory protein of 94 amino acids (PSP94) is a target gene of the EZH2 transcriptional repressor and is often downregulated in prostate cancer; however, its prognostic value is disputed.

METHODS

Immunohistochemical analysis of a tissue microarray of 12, 432 prostate cancer specimens was performed to evaluate PSP94 expression. Correlation of PSP94 expression with tumor phenotype, patient prognosis, fusion status, EZH2 expression and deletion was studied.

RESULTS

PSP94 expression was increased in benign prostatic hyperplasia; however, it was downregulated in 48% and negative in 42% of the 9, 881 interpretable prostate cancer specimens. The loss of PSP94 expression was inversely correlated to EZH2 expression ( < 0.0001) and largely unrelated to the ERG status, but strongly correlated with high Gleason grade, advanced tumor stage, and nodal metastasis ( <0.0001 each). The fraction of PSP94-negative cancer specimens increased from 40% in pT2 to 52% in pT3b-pT4 ( < 0.0001) and from 40% in Gleason 3+3 = 6 to 46% in Gleason 4+3 = 7 and 60% in Gleason ≥4+4 = 8 ( < 0.0001). Loss of PSP94 was linked to early prostate-specific antigen recurrence, but with little absolute effect ( < 0.0001). However, it provided additional prognostic impact in cancer specimens with deletion. Loss of PSP94 deteriorated prognosis of cancer patients with deletion by more than 10% ( < 0.0001). The combination of deletion and PSP94 loss provided independent prognostic information that was observed in several subgroups defined by classical and quantitative Gleason grade.

CONCLUSIONS

The results of our study suggest that combined PSP94/PTEN analysis can be potentially used in the clinical prognosis of prostate cancer.

摘要

目的

94个氨基酸的前列腺分泌蛋白（PSP94）是EZH2转录抑制因子的一个靶基因，在前列腺癌中常被下调；然而，其预后价值存在争议。

方法

对12432例前列腺癌标本的组织芯片进行免疫组化分析，以评估PSP94的表达。研究了PSP94表达与肿瘤表型、患者预后、融合状态、EZH2表达及缺失情况的相关性。

结果

PSP94在良性前列腺增生中表达增加；然而，在9881例可解释的前列腺癌标本中，48%的标本PSP94表达下调，42%的标本为阴性。PSP94表达缺失与EZH2表达呈负相关（<0.0001），与ERG状态基本无关，但与高Gleason分级、肿瘤晚期和淋巴结转移密切相关（均<0.0001）。PSP94阴性的癌标本比例从pT2期的40%增加到pT3b - pT4期的52%（<0.0001），从Gleason 3+3 = 6的40%增加到Gleason 4+3 = 7的46%以及Gleason≥4+4 = 8的60%（<0.0001）。PSP94缺失与前列腺特异性抗原早期复发相关，但绝对影响较小（<0.0001）。然而，它在PTEN缺失的癌标本中提供了额外的预后影响。PSP94缺失使PTEN缺失的癌症患者预后恶化超过10%（<0.0001）。PTEN缺失和PSP94缺失的联合提供了独立的预后信息，在由经典和定量Gleason分级定义的几个亚组中均有观察到。