Reduced AZGP1 expression is an independent predictor of early PSA recurrence and associated with ERG-fusion positive and PTEN deleted prostate cancers
Reduced AZGP1 expression is an independent predictor of early PSA recurrence and associated with ERG-fusion positive and PTEN deleted prostate cancers
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DOI：
10.1002/ijc.29860
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发表时间：
2016-03-01
影响因子：
6.4
通讯作者：
Steurer, Stefan
中科院分区：
文献类型：
--
作者：
Burdelski, Christoph;Kleinhans, Sandra;Steurer, Stefan
锌- α 2糖蛋白（AZGP1）参与脂质代谢，被认为是前列腺癌预后的候选生物标志物。为了评估AZGP1的临床影响及其与前列腺癌关键基因组改变的关系，我们在包含11,152例前列腺癌的组织微阵列上通过免疫组化分析AZGP1的表达。ERG状态和PTEN、3p13、5q21和6q15缺失的数据可从早期研究中获得。AZGP1在良性前列腺中表达强烈，但在8,510例可解释的前列腺癌中不表达。通过FISH和免疫组织化学分析，AZGP1表达降低与TPMRSS2: ERG融合相关（p < 0.0001）。例如，在2029例ERG IHC阳性患者中，54.6%的患者不存在AZGP1，但在2398例ERG阴性患者中，只有28.1%的患者不存在AZGP1。无论ERG状态如何，AZGP1表达降低与高Gleason评分、晚期病理肿瘤分期、淋巴结阳性状态和早期PSA复发密切相关（p < 0.0001）。AZGP1表达减少也与PTEN缺失密切相关。在842例PTEN缺失的患者中，62.7%缺乏AZGP1免疫染色，而在PTEN未缺失的患者中，只有37.3%缺乏AZGP1免疫染色，但在两个亚组中都有很强的预后影响（p < 0.0001）。AZGP1表达的预后作用也与Gleason评分、pT分期、pN分期、手术切缘状态和术前PSA无关，与术前或术后变量是否用于建模无关。总之，我们的研究结果表明，AZGP1表达的降低与前列腺癌的不良预后密切相关，独立于既定的临床病理变量和PTEN缺失。
Zinc-alpha 2-glycoprotein (AZGP1) is involved in lipid metabolism and was suggested as a candidate prognostic biomarker in prostate cancer. To evaluate the clinical impact and relationship with key genomic alterations in prostate cancer, AZGP1 expression was analyzed by immunohistochemistry on a tissue microarray containing 11,152 prostate cancers. Data on ERG status and PTEN, 3p13, 5q21 and 6q15 deletions were available from earlier studies. AZGP1 expression was strong in benign prostatic glands but absent in 38.0% of 8,510 interpretable prostate cancers. Reduced AZGP1 expression was associated with TPMRSS2: ERG fusions, both by FISH and immunohistochemical analysis (p < 0.0001 each). For example, AZGP1 was absent in 54.6% of 2,029 ERG IHC positive but in only 28.1% of 2,398 ERG negative cancers. Irrespective of the ERG status, reduced AZGP1 expression was tightly linked to high Gleason score, advanced pathological tumor stage, positive nodal status and early PSA recurrence (p < 0.0001 each). Reduced AZGP1 expression was also strongly associated with PTEN deletions. AZGP1 immunostaining was lacking in 62.7% of 842 PTEN deleted but in only 37.3% of PTEN non-deleted cancers but retained strong prognostic influence in both subgroups (p < 0.0001 each). The prognostic role of AZGP1 expression was also independent of Gleason score, pT stage, pN stage, surgical margin status and preoperative PSA, irrespective of whether preoperative or postoperative variables were used for modeling. In conclusion, the results of our study demonstrate that reduced AZGP1 expression is strongly related to adverse prostate cancer prognosis, independently of established clinic-pathological variables and PTEN deletions.