Protein Expression of PTTG1 as a Diagnostic Biomarker in Adrenocortical Carcinoma
Protein Expression of PTTG1 as a Diagnostic Biomarker in Adrenocortical Carcinoma
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DOI：
10.1245/s10434-017-6297-1
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发表时间：
2018-03-01
影响因子：
3.7
通讯作者：
Demeure, Michael J.
中科院分区：
文献类型：
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作者：
Arenas, Minerva Angelica Romero;Whitsett, Timothy G.;Demeure, Michael J.
肾上腺皮质癌（ACC）预后不良，临床上需要生物标志物来改善诊断和预后评估。垂体肿瘤转化基因（PTTG 1）已被证明可以调节癌症的侵袭性和对治疗的反应。PTTG 1蛋白水平在ACC中的潜在作用以前尚未得到解决。我们评估了PTTG 1核蛋白表达的增加是否能区分ACC和肾上腺皮质腺瘤（ACA）。ACC或ACA患者来自两个独立机构的预期组织库。两个组织微阵列（TMA）组成的肾上腺标本从131例患者的构建和临床注释。TMA-1组（n = 80）包括20例正常肾上腺、20例ACA和40例ACC; TMA-2组（n = 51）包括10例正常肾上腺、14例ACA和27例ACC。在TMA-1上，12例（31%）ACC标本中检测到PTTG 1的核染色，而所有ACA和正常肾上腺均为PTTG 1阴性。在TMA-2上，20例（74%）ACC肿瘤显示PTTG 1核染色，13例（93%）ACA和4例（44%）正常肾上腺PTTG 1阴性。PTTG 1蛋白阳性表达的ACC肿瘤Ki-67指数显著高于PTTG 1蛋白阴性表达的ACC肿瘤（P < 0.001）。PTTG 1与Ki-67在两个独立的TMA中相关。PTTG 1在肾上腺肿瘤的诊断中具有重要的临床应用价值。
Adrenocortical carcinoma (ACC) has a poor prognosis and there is an unmet clinical need for biomarkers to improve both diagnostic and prognostic assessment. Pituitary-tumor transforming gene (PTTG1) has been shown to modulate cancer invasiveness and response to therapy. The potential role of PTTG1 protein levels in ACC has not been previously addressed. We assessed whether increased nuclear protein expression of PTTG1 distinguished ACCs from adrenocortical adenomas (ACAs).Patients with ACC or ACA were identified from prospective tissue banks at two independent institutions. Two tissue microarrays (TMAs) consisting of adrenal specimens from 131 patients were constructed and clinically annotated. Immunohistochemical analysis for PTTG1 and Ki-67 was performed on each TMA.TMA-1 (n = 80) contained 20 normal adrenals, 20 ACAs, and 40 ACCs, and the validation, TMA-2 (n = 51), consisted of 10 normal adrenals, 14 ACAs, and 27 ACCs. On TMA-1, nuclear staining of PTTG1 was detected in 12 (31%) ACC specimens, while all ACAs and normal adrenal glands were negative for PTTG1. On TMA-2, 20 (74%) of the ACC tumors demonstrated PTTG1 nuclear staining of PTTG1, and 13 (93%) ACA and 4 (44%) normal adrenal glands were negative for PTTG1. ACC tumors with increased PTTG1 protein staining had a significantly higher Ki-67 index (p < 0.001) than those with lower levels of PTTG1.Increased nuclear protein expression of PTTG1 was observed in malignant adrenal tumors. PTTG1 correlated with Ki-67 in two independent TMAs. PTTG1 is a promising biologic marker in the evaluation of adrenal tumors.