Department of Urology, University Hospital, University of Zurich, Zurich, Switzerland.
Department of Pathology of Molecular Pathology, University Hospital, University of Zurich, Zurich, Switzerland.
BMC Cancer. 2019 Aug 14;19(1):802. doi: 10.1186/s12885-019-5961-1.
To validate the utility of the chemokine ligand 12 (CXCL12) as prognostic marker in patients with localized and metastatic germ cell tumors (GCT).
CXCL12 expression was analyzed on a tissue microarray consisting of 750 tissue cores of different histological tumor components, Germ cell neoplasia in situ (GCNIS) and adjacent normal tissue of 263 testicular cancer patients using a semi-quantitative score. The association between CXCL12 expression and recurrence-free survival (RFS) as well as overall survival (OS) was assessed using Kaplan-Meier curves with log-rank tests.
CXCL12 expression was absent in all seminomas but was found in 52 of 99 (52.5%) non-seminomas. Follow-up was available for 260 patients of which 36 (13.8%) recurred. In patients with stage 1 non-seminoma GCT, CXCL12 expression was not associated with higher risk of disease recurrence (p = 0.270). In contrast, post chemotherapy RFS of patients with metastatic non-seminoma and positive CXCL12 expression was significantly shorter compared to CXCL12 negative patients (p = 0.003). OS differences were not statistically different between patients with CXCL12 positive or negative tumors for either localized or metastatic disease.
CXCL12 is almost exclusively expressed in non-seminoma. Pure seminoma, GCNIS and adjacent normal testicular tissue are CXCL12 negative. Our analysis suggests that patients with metastatic disease and a CXCL12-positive non-seminoma are at higher risk for disease recurrence after first-line chemotherapy and might thus be candidates for more intensive treatment and/or closer follow-up.
验证趋化因子配体 12(CXCL12)作为局限性和转移性生殖细胞瘤(GCT)患者预后标志物的效用。
使用半定量评分法,对 263 例睾丸癌患者的组织微阵列进行分析,该微阵列包含 750 个不同组织学肿瘤成分、生殖细胞原位肿瘤(GCNIS)和相邻正常组织的组织芯。使用 Kaplan-Meier 曲线和对数秩检验评估 CXCL12 表达与无复发生存(RFS)和总生存(OS)之间的关联。
所有精原细胞瘤均无 CXCL12 表达,但 99 例非精原细胞瘤中有 52 例(52.5%)有 CXCL12 表达。对 260 例患者进行了随访,其中 36 例(13.8%)复发。在 1 期非精原细胞瘤 GCT 患者中,CXCL12 表达与疾病复发风险增加无关(p=0.270)。相比之下,化疗后转移性非精原细胞瘤患者中 CXCL12 阳性患者的 RFS 明显短于 CXCL12 阴性患者(p=0.003)。对于局限性或转移性疾病,CXCL12 阳性或阴性肿瘤的患者 OS 差异无统计学意义。
CXCL12 几乎仅在非精原细胞瘤中表达。纯精原细胞瘤、GCNIS 和相邻正常睾丸组织均为 CXCL12 阴性。我们的分析表明,一线化疗后转移性疾病和 CXCL12 阳性非精原细胞瘤患者疾病复发的风险更高,因此可能是更强化疗和/或更密切随访的候选者。