Department of Pathology, The First Affiliated Hospital of Medical School of Xi'an Jiaotong University, Xi'an, China.
J Clin Pathol. 2012 Dec;65(12):1088-96. doi: 10.1136/jclinpath-2012-200940. Epub 2012 Sep 3.
Cortactin acts as a prominent substrate of histone deacetylases (HDACs) and plays important roles in tumour progression in several human cancers. However, the clinical significance of its expression in human prostate cancer (PCa) has not been determined. We aimed to identify the potential role of cortactin expression in tumour progression and prognosis in PCa and the association with HDACs.
256 foci with distinctive lesions in 110 prostate specimens were collected to identify the status of among cortactin, SIRT2, histone deacetylase 6 (HDAC6) by immunohistochemistry and its relationship with clinicopathological and follow-up data were analysed.
The results showed that cortactin expression was significantly higher (79.1%), and SIRT2 expression was lower (37.3%) in PCa foci, when it was compared with high-grade prostatic intraepithelial neoplasia foci and benign foci, respectively. HDAC6 expression was low and had no statistical significance in PCa. High intensity of cortactin staining was significantly and independently associated with a high prostate-specific antigen (PSA) level, high Gleason score, clinical stage progression and shortened survival time in patients with PCa. High intensity of SIRT2 staining was significantly and independently associated with a high PSA level, old age, high Gleason score and clinical stage progression. Multivariable Cox regression analysis showed cortactin expression was a significant prognostic factor for survival of patients with PCa (β, 0.736; 95% CI 1.371 to 3.181; p=0.001).
The results suggested that cortactin seems to be a satisfactory marker to predict tumour progression and survival in cases of PCa. And it may be SIRT2 rather than HADAC6 is responsible for tumour occurrence and the progression of PCa.
桩蛋白作为组蛋白去乙酰化酶（HDACs）的重要底物，在几种人类癌症的肿瘤进展中发挥重要作用。然而，其在人前列腺癌（PCa）中的表达的临床意义尚未确定。我们旨在确定桩蛋白表达在 PCa 肿瘤进展和预后中的潜在作用及其与 HDACs 的关联。
收集 110 例前列腺标本中具有明显病变的 256 个病灶，通过免疫组织化学方法确定桩蛋白、SIRT2、组蛋白去乙酰化酶 6（HDAC6）的状态，并分析其与临床病理和随访数据的关系。
结果表明，与高级别前列腺上皮内瘤变病灶和良性病灶相比，PCa 病灶中桩蛋白表达明显升高（79.1%），SIRT2 表达降低（37.3%）。HDAC6 表达较低，无统计学意义。桩蛋白染色强度高与 PCa 患者前列腺特异性抗原（PSA）水平高、Gleason 评分高、临床分期进展和生存时间缩短显著相关。SIRT2 染色强度高与 PSA 水平高、年龄大、Gleason 评分高和临床分期进展显著相关。多变量 Cox 回归分析显示，桩蛋白表达是 PCa 患者生存的显著预后因素（β，0.736；95%CI 1.371 至 3.181；p=0.001）。
结果表明，桩蛋白似乎是预测 PCa 肿瘤进展和生存的一个满意标志物。而且可能是 SIRT2 而不是 HADAC6 负责 PCa 的发生和进展。
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