Progranulin (GP88) tumor tissue expression is associated with increased risk of recurrence in breast cancer patients diagnosed with estrogen receptor positive invasive ductal carcinoma.
Progranulin (GP88) tumor tissue expression is associated with increased risk of recurrence in breast cancer patients diagnosed with estrogen receptor positive invasive ductal carcinoma.
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DOI：
10.1186/bcr3111
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发表时间：
2012-02-08
期刊：
影响因子：
--
通讯作者：
Kim WE
中科院分区：
文献类型：
--
作者：
Serrero G;Hawkins DM;Yue B;Ioffe O;Bejarano P;Phillips JT;Head JF;Elliott RL;Tkaczuk KR;Godwin AK;Weaver J;Kim WE
GP88（颗粒体蛋白前体）与雌激素受体阳性 (ER+) 乳腺癌的肿瘤发生和抗雌激素治疗耐药有关。既往病理研究表明，GP88在浸润性导管癌（IDC）中表达，但在正常乳腺上皮组织、良性病变或小叶癌中不表达。基于这些结果，本研究检查了 GP88 与 ER+ IDC 患者复发和死亡风险相关的预后意义。两项回顾性多中心临床研究通过对 ER+ IDC 患者（淋巴结阳性和阴性，1 至 3 期）的石蜡包埋乳腺肿瘤组织切片进行免疫组织化学 (IHC) 分析，检查了 GP88 表达与患者生存结果的相关性。训练研究建立了与无病生存率 (DFS) 和总生存率 (OS) 下降相关的 GP88 截止值。验证研究验证了 GP88 截止值，并将 GP88 预后信息与其他预后因素进行比较，特别是多变量分析中的肿瘤大小、分级、疾病阶段和淋巴结状态。 GP88 表达与 ER+ IDC 患者复发风险的统计显着增加相关。培训研究证实 GP88 3+ 评分与 DFS (P = 0.0004) 和 OS (P = 0.0036) 下降相关。独立验证研究证实，与肿瘤 GP88 < 3+ 的患者相比，GP88 3+ 评分的疾病复发风险高出 5.9 倍，死亡风险高出 2.5 倍。在考虑年龄、种族、淋巴结状态、肿瘤大小、肿瘤分级、疾病阶段、孕激素受体表达和治疗后，GP88 仍然是独立的风险预测因子。生存因子 GP88 是一种新型预后生物标志物，可预测非转移性 ER+ IDC 患者的复发风险和死亡率增加。重要的是，我们的数据表明，即使五年后，GP88 仍然是一个预后因素。这些结果还提供了证据，表明 GP88 提供了独立于肿瘤和临床特征的预后信息，并将支持前瞻性研究，以检查 GP88 表达是否有助于对 ER+ 肿瘤患者进行分层以进行辅助治疗。
GP88 (progranulin) has been implicated in tumorigenesis and resistance to anti-estrogen therapies for estrogen receptor positive (ER+) breast cancer. Previous pathological studies showed that GP88 is expressed in invasive ductal carcinoma (IDC), but not in normal mammary epithelial tissue, benign lesions or lobular carcinoma. Based on these results, the present study examines GP88 prognostic significance in association with recurrence and death risks for ER+ IDC patients. Two retrospective multi-site clinical studies examined GP88 expression by immunohistochemistry (IHC) analysis of paraffin-embedded breast tumor tissue sections from ER+ IDC patients (lymph node positive and negative, stage 1 to 3) in correlation with patients' survival outcomes. The training study established a GP88 cut-off value associated with decreased disease-free (DFS) and overall (OS) survivals. The validation study verified the GP88 cut-off value and compared GP88 prognostic information with other prognostic factors, particularly tumor size, grade, disease stage and lymph node status in multivariate analysis. GP88 expression is associated with a statistically significant increase in recurrence risk for ER+ IDC patients. The training study established that GP88 3+ score was associated with decreased DFS (P = 0.0004) and OS (P = 0.0036). The independent validation study verified that GP88 3+ score was associated with a 5.9-fold higher hazard of disease recurrence and a 2.5-fold higher mortality hazard compared to patients with tumor GP88 < 3+. GP88 remained an independent risk predictor after considering age, ethnicity, nodal status, tumor size, tumor grade, disease stage, progesterone receptor expression and treatments. The survival factor GP88 is a novel prognostic biomarker, predictive of recurrence risk and increased mortality for non-metastatic ER+ IDC patients. Of importance, our data show that GP88 continues to be a prognostic factor even after five years. These results also provide evidence that GP88 provides prognostic information independent of tumor and clinical characteristics and would support prospective study to examine whether GP88 expression could help stratify patients with ER+ tumors for adjuvant therapy.
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82.9
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