Brownhill Samantha, Cohen Dena, Burchill Sue
Children's Cancer Research Group, Leeds Institute of Cancer and Pathology, St James's University Hospital, Leeds, United Kingdom.
Clinical Trials Research Unit, Leeds Institute of Cancer and Pathology, St James's University Hospital, Leeds, United Kingdom.
PLoS One. 2014 Aug 26;9(8):e104106. doi: 10.1371/journal.pone.0104106. eCollection 2014.
The prognostic value of proliferation index (PI) and apoptotic index (AI), caspase-8, -9 and -10 expression have been investigated in primary Ewing's sarcoma family of tumours (ESFT). Proliferating cells, detected by immunohistochemistry for Ki-67, were identified in 91% (91/100) of tumours with a median PI of 14 (range 0-87). Apoptotic cells, identified using the TUNEL assay, were detected in 96% (76/79) of ESFT; the median AI was 3 (range 0-33). Caspase-8 protein expression was negative (0) in 14% (11/79), low (1) in 33% (26/79), medium (2) in 38% (30/79) and high (3) in 15% (12/79) of tumours, caspase-9 expression was low (1) in 66% (39/59) and high (3) in 34% (20/59), and caspase-10 protein was low (1) in 37% (23/62) and negative (0) in 63% (39/62) of primary ESFT. There was no apparent relationship between caspase-8, -9 and -10 expression, PI and AI. PI was predictive of relapse-free survival (RFS; p = 0.011) and overall survival (OS; p = <0.001) in a continuous model, whereas AI did not predict outcome. Patients with tumours expressing low levels of caspase-9 protein had a trend towards a worse RFS than patients with tumours expressing higher levels of caspase-9 protein (p = 0.054, log rank test), although expression of caspases-8, -9 and/or -10 did not significantly predict RFS or OS. In a multivariate analysis model that included tumour site, tumour volume, the presence of metastatic disease at diagnosis, PI and AI, PI independently predicts OS (p = 0.003). Consistent with previous publications, patients with pelvic tumours had a significantly worse OS than patients with tumours at other sites (p = 0.028); patients with a pelvic tumour and a PI≥20 had a 6 fold-increased risk of death. These studies advocate the evaluation of PI in a risk model of outcome for patients with ESFT.
在原发性尤因肉瘤家族性肿瘤（ESFT）中，研究了增殖指数（PI）、凋亡指数（AI）、半胱天冬酶-8、-9和-10表达的预后价值。通过免疫组织化学检测Ki-67来检测增殖细胞，在91%（91/100）的肿瘤中检测到增殖细胞，PI中位数为14（范围0-87）。使用TUNEL法鉴定凋亡细胞，在96%（76/79）的ESFT中检测到凋亡细胞；AI中位数为3（范围0-33）。在14%（11/79）的肿瘤中，半胱天冬酶-8蛋白表达为阴性（0），33%（26/79）为低表达（1），38%（30/79）为中等表达（2），15%（12/79）为高表达（3）；66%（39/59）的半胱天冬酶-9表达为低表达（1），34%（20/59）为高表达（3）；在原发性ESFT中，37%（23/62）的半胱天冬酶-10蛋白为低表达（1），63%（39/62）为阴性（0）。半胱天冬酶-8、-9和-10表达、PI和AI之间没有明显关系。在连续模型中，PI可预测无复发生存期（RFS；p = 0.011）和总生存期（OS；p = <0.001），而AI不能预测预后。与表达较高水平半胱天冬酶-9蛋白的患者相比，表达低水平半胱天冬酶-9蛋白的肿瘤患者的RFS有变差的趋势（p = 0.054，对数秩检验），尽管半胱天冬酶-8、-9和/或-10的表达不能显著预测RFS或OS。在一个包括肿瘤部位、肿瘤体积、诊断时是否存在转移性疾病、PI和AI的多变量分析模型中，PI独立预测OS（p = 0.003）。与既往出版物一致，盆腔肿瘤患者的OS明显比其他部位肿瘤患者差（p = 0.028）；盆腔肿瘤且PI≥20的患者死亡风险增加6倍。这些研究主张在ESFT患者的预后风险模型中评估PI。
