Impact of SYT-SSX fusion type on the clinical behavior of synovial sarcoma: a multi-institutional retrospective study of 243 patients.-猫眼课题宝

DOI：

发表时间：

2002

期刊：

Cancer research

影响因子：

11.2

通讯作者：

中科院分区：

医学1区

文献类型：

作者：

M. Ladanyi;C. Antonescu;D. Leung;J. Woodruff;A. Kawai;J. Healey;M. Brennan;J. Bridge;J. Neff;F. Barr;J. Goldsmith;J. Brooks;J. Goldblum;Syed Z. Ali;J. Shipley;C. Cooper;C. Fisher;B. Skytting;O. Larsson

滑膜肉瘤是侵袭性的梭形细胞肉瘤，在某些情况下含有上皮分化区。它们一致显示一个特定的t(X；18；p11；q11)，通常代表两个基因融合中的一个，SYT-SSX1或SYT-SSX2，编码13个氨基酸位置的假定转录蛋白。以前的研究表明，患有SYT-SSX2肿瘤的患者比患有SYT-SSX1肿瘤的患者表现更好，但研究小组太有限，无法得出结论。为了更明确地解决这个问题，我们收集了关于SYT-SSX融合类型、病理和临床病程的数据，对243名滑膜肉瘤患者(年龄范围为6-82岁)进行了回顾性多机构研究。SYT-SSX1融合147例(61%)，SYT-SSX2融合91例(37%)。组织学上，根据腺上皮分化区的存在与否，61例(25%)为双相型，180例(74%)为单相型。SYT-SSX1和SYT-SSX2组的中位生存期和5年生存率分别为6.1年和53%，13.7年和73%。本组病例的总体生存率显著高于初诊病例(P=0.0001.0 1)和原发肿瘤最大直径<5 cm的病例(P=0.0 1)。年龄、性别、组织学类型、轴向与外周原发部位对总存活率无影响。当按原发肿瘤大小分层时，融合类型对存活率的影响仍然显著(P=0.03)，但当按出现时的疾病状态分层时，融合类型对生存率的影响不再显着。这可能反映了SYT-SSX1肿瘤患者更容易出现转移性疾病(P=0.05)。COX回归确定疾病状态(P&lt；0.0001)和原发肿瘤大小(P=0.04)是160例患者中独立预测总体生存的唯一因素。在确诊时有局部疾病的患者(n=202)中，SYT-SSX1组和SYT-SSX2组的中位生存期和5年生存率分别为9.2年和61%，而SYT-SSX2组分别为13.7年和77%。肿瘤中含有SYT-SSX2融合基因(P=0.08)或较小(P=0.12)的患者经log-ranch检验有较好的生存趋势，而肿瘤组织学无明显影响(P=0.8)。在考虑所有因素的Cox回归分析中，SYT-SSX融合型是133例确诊时已了解所有因素的局部性疾病患者的总生存率的唯一独立显著因素(P=0.04)。在其他比较中，融合类型和形态有很强的相关性(P&lt；0.001)，几乎所有的SYT-SSX2肿瘤都没有腺体分化(单相组织学)，几乎所有的双相肿瘤都含有SYT-SSX1。融合类型与患者性别的相关性也有统计学意义(P=0.03)，SYT-SSX1患者的男女比例为1：1，而SYT-SSX2患者的男女比例接近1：2。经多因素分析，SYT-SSX融合类型似乎是单一的最显著预后因素。SYT-SSX融合型在发病前似乎也通过与诊断阶段的关联而对预后产生部分影响。此外，SYT-SSX融合类型与患者性别和肿瘤上皮细胞分化的关系指向有趣的机制生物学差异。

Synovial sarcomas are aggressive spindle cell sarcomas containing in some cases areas of epithelial differentiation. They consistently show a specific t(X;18;p11;q11), which usually represents either of two gene fusions, SYT-SSX1 or SYT-SSX2, encoding putative transcriptional proteins differing at 13 amino acid positions. Previous studies have suggested that patients with SYT-SSX2 tumors do better than those with SYT-SSX1 tumors, but the study groups were too limited to be conclusive. To address this issue more definitively, we collected data on SYT-SSX fusion type, pathology, and clinical course in a retrospective multi-institutional study of 243 patients (age range, 6-82) with synovial sarcoma. SYT-SSX1 and SYT-SSX2 fusions were detected in 147 tumors (61%) and 91 tumors (37%), respectively. Histologically, 61 (25%) were classified as biphasic type and 180 (74%) as monophasic type based on the presence or absence of areas of glandular epithelial differentiation, respectively. Median and 5-year overall survivals for the SYT-SSX1 and SYT-SSX2 groups were 6.1 years and 53%, and 13.7 years and 73%, respectively. Overall survival was significantly better among SYT-SSX2 cases (P = 0.03), among cases localized at diagnosis (P < 0.0001), and among patients with primary tumors < 5 cm in greatest dimension (P = 0.01). Age, sex, histological type, and axial versus peripheral primary site had no impact on overall survival. The impact of fusion type on survival remained significant when stratified for primary tumor size (P = 0.03) but was no longer significant when stratified for disease status at presentation. This may reflect the tendency for patients with SYT-SSX1 tumors to present more often with metastatic disease (P = 0.05). Cox regression identified disease status (P < 0.0001) and primary tumor size (P = 0.04) as the only factors independently predictive of overall survival in the subset of 160 patients with information on all of the factors. Within the subset of patients with localized disease at diagnosis (n = 202), the median and 5-year survival for the SYT-SSX1 and the SYT-SSX2 groups were 9.2 years and 61% versus 13.7 years and 77%, respectively. Patients whose tumors contained the SYT-SSX2 fusion (P = 0.08) or were smaller (P = 0.12) showed a trend toward better survival by log-rank test, whereas tumor histology had no impact (P = 0.8). In a Cox regression analysis considering all of the factors, SYT-SSX fusion type emerged as the only independent significant factor (P = 0.04) for overall survival within the subset of 133 patients with localized disease at diagnosis who had information on all of the factors. Among other comparisons, there was a strong association of fusion type and morphology (P < 0.001), with almost all of the SYT-SSX2 tumors showing absence of glandular differentiation (monophasic histology) and almost all of the biphasic tumors containing SYT-SSX1. There was also a statistically significant association of fusion type and patient sex (P = 0.03); specifically, the male:female ratio of SYT-SSX1 cases was 1:1, whereas for SYT-SSX2 cases, it was close to 1:2. Overall, SYT-SSX fusion type appears to be the single most significant prognostic factor by multivariate analysis in patients with localized disease at diagnosis. SYT-SSX fusion type also appears to exert part of its impact on prognosis before presentation through its association with stage at diagnosis. In addition, the associations of SYT-SSX fusion type with patient sex and tumor epithelial differentiation point to interesting mechanistic biological differences.

Impact of SYT-SSX fusion type on the clinical behavior of synovial sarcoma: a multi-institutional retrospective study of 243 patients.

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