Prognostic value of mitotic checkpoint protein BUB3, cyclin B1, and pituitary tumor-transforming 1 expression in prostate cancer.,Modern Pathology

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Prognostic value of mitotic checkpoint protein BUB3, cyclin B1, and pituitary tumor-transforming 1 expression in prostate cancer.
Modern Pathology ( IF 7.1 ) Pub Date : 2019-12-04 , DOI: 10.1038/s41379-019-0418-2
Elin Ersvær ₁ , Wanja Kildal ₁ , Ljiljana Vlatkovic ₂ , Karolina Cyll ₁ , Manohar Pradhan ₁ , Andreas Kleppe _{1,

3} , Tarjei S Hveem ₁ , Hanne A Askautrud ₁ , Marco Novelli _{1,

4} , Håkon Wæhre ₁ , Knut Liestøl _{1,

3} , Håvard E Danielsen _{1,

3,

5}

Affiliation

The mitotic checkpoint protein BUB3, cyclin B1 (CCNB1) and pituitary tumor-transforming 1 (PTTG1) regulates cell division, and are sparsely studied in prostate cancer. Deregulation of these genes can lead to genomic instability, a characteristic of more aggressive tumors. We aimed to determine the expression levels of BUB3, CCNB1, and PTTG1 as potential prognostic markers of recurrence after radical prostatectomy. Protein levels were determined by immunohistochemistry on three formalin-fixed paraffin-embedded tissue sections from each of the 253 patients treated with radical prostatectomy. Immunohistochemistry scores were obtained by automated image analysis for CCNB1 and PTTG1. Recurrence, defined as locoregional recurrence, distant metastasis or death from prostate cancer, was used as endpoint for survival analysis. Tumors having both positive and negative tumor areas for cytoplasmic BUB3 (30%), CCNB1 (28%), or PTTG1 (35%) were considered heterogeneous. Patients with ≥1 positive tumor area had significantly increased risk of disease recurrence in univariable analysis compared with patients where all tumor areas were negative for cytoplasmic BUB3 (hazard ratio [HR] = 2.18, 95% confidence interval [CI] 1.41-3.36), CCNB1 (HR = 2.98, 95% CI 1.93-4.61) and PTTG1 (HR = 1.91, 95% CI 1.23-2.97). Combining the scores of cytoplasmic BUB3 and CCNB1 improved risk stratification when integrated with the Cancer of the Prostate Risk Assessment post-Surgical (CAPRA-S) score (difference in concordance index = 0.024, 95% CI 0.001-0.05). In analysis of multiple tumor areas, prognostic value was observed for cytoplasmic BUB3, CCNB1, and PTTG1.

中文翻译：

前列腺癌中有丝分裂检查点蛋白 BUB3、细胞周期蛋白 B1 和垂体肿瘤转化 1 表达的预后价值。

有丝分裂检查点蛋白 BUB3、细胞周期蛋白 B1 (CCNB1) 和垂体肿瘤转化蛋白 1 (PTTG1) 调节细胞分裂，在前列腺癌中的研究很少。这些基因的失调会导致基因组不稳定，这是更具侵袭性的肿瘤的一个特征。我们旨在确定 BUB3、CCNB1 和 PTTG1 的表达水平作为根治性前列腺切除术后复发的潜在预后标志物。通过免疫组织化学对 253 名接受根治性前列腺切除术治疗的患者的三个福尔马林固定石蜡包埋组织切片的蛋白质水平进行测定。通过 CCNB1 和 PTTG1 的自动图像分析获得免疫组织化学评分。复发，定义为局部区域复发、远处转移或前列腺癌死亡，被用作生存分析的终点。具有细胞质 BUB3 (30%)、CCNB1 (28%) 或 PTTG1 (35%) 阳性和阴性肿瘤区域的肿瘤被认为是异质的。与所有肿瘤区域细胞质 BUB3 均为阴性的患者相比，单变量分析中≥1 个阳性肿瘤区域的患者疾病复发风险显着增加（风险比 [HR] = 2.18，95% 置信区间 [CI] 1.41-3.36）， CCNB1（HR = 2.98，95% CI 1.93-4.61）和 PTTG1（HR = 1.91，95% CI 1.23-2.97）。将细胞质 BUB3 和 CCNB1 的评分与手术后前列腺癌风险评估 (CAPRA-S) 评分相结合可改善风险分层（一致性指数的差异 = 0.024，95% CI 0.001-0.05）。在多个肿瘤区域的分析中，观察到细胞质 BUB3、CCNB1 和 PTTG1 的预后价值。

更新日期：2019-12-04

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