Phospho-Akt Immunoreactivity in Prostate Cancer: Relationship to Disease Severity and Outcome, Ki67 and Phosphorylated EGFR Expression
Phospho-Akt Immunoreactivity in Prostate Cancer: Relationship to Disease Severity and Outcome, Ki67 and Phosphorylated EGFR Expression
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DOI：
10.1371/journal.pone.0047994
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发表时间：
2012-10-25
期刊：
影响因子：
3.7
通讯作者：
Fowler, Christopher J.
中科院分区：
文献类型：
--
作者：
Hammarsten, Peter;Cipriano, Mariateresa;Fowler, Christopher J.
背景：在本研究中，我们利用表征良好的组织微阵列研究了磷酸化Akt免疫反应性（pAkt-IR）在前列腺癌中的预后价值，这些前列腺癌患者因下尿路症状而接受了经尿道切除术。方法/主要发现：使用单克隆抗pakt （Ser(473)）抗体评估前列腺上皮细胞和肿瘤细胞中的pAkt-IR。282例（肿瘤）和240例（非恶性组织）测定了免疫反应强度。肿瘤pAkt-IR评分与Gleason评分、肿瘤Ki67-IR（细胞增殖标志物）和肿瘤磷酸化表皮生长因子受体(pEGFR)-IR相关。对于预期随访的病例，高肿瘤pAkt-IR与较差的疾病特异性生存率相关，该生物标志物提供的预后信息与肿瘤pEFGR-IR或Ki67-IR（但不是两者都提供）提供的预后信息是附加的。根据Gleason评分对病例进行分组后发现，pAkt-IR对Gleason评分为8-10分的患者有预后价值，而对Gleason评分为6-7分的患者没有预后价值。结论/意义：肿瘤pAkt-IR与疾病严重程度和疾病特异性生存相关。然而，它作为生物标志物的临床应用是有限的，因为它不能提供Gleason评分为6-7的患者的预后信息。
Background: In the present study, we have investigated the prognostic usefulness of phosphorylated Akt immunoreactivity (pAkt-IR) in prostate cancer using a well-characterised tissue microarray from men who had undergone transurethral resection due to lower urinary tract symptoms.Methodology/Principal Findings: pAkt-IR in prostate epithelial and tumour cells was assessed using a monoclonal anti-pAkt (Ser(473)) antibody. Immunoreactive intensity was determined for 282 (tumour) and 240 (non-mlignant tissue) cases. Tumour pAkt-IR scores correlated with Gleason score, tumour Ki67-IR (a marker of cell proliferation) and tumour phosphorylated epidermal growth factor receptor (pEGFR)-IR. For cases followed with expectancy, a high tumour pAkt-IR was associated with a poor disease-specific survival, and the prognostic information provided by this biomarker was additive to that provided by either (but not both) tumour pEFGR-IR or Ki67-IR. Upon division of the cases with respect to their Gleason scores, the prognostic value of pAkt-IR was seen for patients with Gleason score 8-10, but not for patients with Gleason score 6-7.Conclusions/Significance: Tumour pAkt-IR is associated with both disease severity and disease-specific survival. However, its clinical use as a biomarker is limited, since it does not provide prognostic information in patients with Gleason scores 6-7.