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生长抑素受体表达与肺类癌肿瘤的转移和患者预后相关。

Somatostatin Receptor Expression Is Associated With Metastasis and Patient Outcome in Pulmonary Carcinoid Tumors.

机构信息

HUSLAB, Department of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland.

出版信息

J Clin Endocrinol Metab. 2019 Jun 1;104(6):2083-2093. doi: 10.1210/jc.2018-01931.

Abstract

CONTEXT

Pulmonary carcinoids (PCs) belong to neuroendocrine tumors that often overexpress somatostatin receptors (SSTRs). This overexpression provides a molecular basis for tumor imaging and treatment with somatostatin analogs.

OBJECTIVE

To evaluate SSTR1 to SSTR5 distribution in a large set of PC tumors and to investigate whether the expression is associated with clinicopathological and outcome data.

DESIGN, SETTING, AND PATIENTS: This retrospective study was conducted at Helsinki University Hospital and University of Helsinki. It included 178 PC tumors coupled with patients' clinical data retrieved through Finnish biobanks. After histological reclassification, tissue specimens were processed into next-generation tissue microarray format and stained immunohistochemically with monoclonal SSTR1 to SSTR5 antibodies.

MAIN OUTCOME MEASURE

SSTR1 to SSTR5 expression in PC tumors.

RESULTS

Expression of SSTR1 to SSTR5 was detected in 52%, 75%, 56%, 16%, and 32% of the tumors, respectively. Membrane-bound staining was observed for all receptors. SSTR2 negativity and SSTR4 positivity was associated with lymph node involvement at the time of surgery (P = 0.014 and P = 0.017, respectively) and with distant metastasis (P = 0.027 and P = 0.015, respectively). SSTR3 and SSTR4 expression was associated with increased risk of shorter survival [P = 0.046, hazard ratio (HR) 4.703, 95% CI 1.027 to 21.533; and P = 0.013, HR 6.64, 95% CI 1.48 to 29.64, respectively], whereas expression of SSTR1 and SSTR2 was associated with improved outcome (P = 0.021, HR 0.167, 95% CI 0.037 to 0.765; and P = 0.022, HR 0.08, 95% CI 0.01 to 0.70, respectively).

CONCLUSION

SSTR1 to SSTR5 expression is observed in PCs. As SSTR expression is associated with the tumor's metastatic potential and patient outcome, these receptors may offer the possibility for individualized prognosis estimation.

摘要

背景

肺类癌(PC)属于神经内分泌肿瘤,常过度表达生长抑素受体(SSTR)。这种过度表达为使用生长抑素类似物进行肿瘤成像和治疗提供了分子基础。

目的

评估一组大样本 PC 肿瘤中 SSTR1 至 SSTR5 的分布,并研究其表达是否与临床病理和预后数据相关。

设计、地点和患者:这项回顾性研究在赫尔辛基大学医院和赫尔辛基大学进行,纳入了与芬兰生物库中检索到的患者临床数据相关联的 178 例 PC 肿瘤。经过组织学重新分类后,组织标本被加工成下一代组织微阵列格式,并使用单克隆 SSTR1 至 SSTR5 抗体进行免疫组织化学染色。

主要观察指标

PC 肿瘤中 SSTR1 至 SSTR5 的表达。

结果

分别在 52%、75%、56%、16%和 32%的肿瘤中检测到 SSTR1 至 SSTR5 的表达。所有受体均观察到膜结合染色。SSTR2 阴性和 SSTR4 阳性与手术时淋巴结受累(P = 0.014 和 P = 0.017)和远处转移(P = 0.027 和 P = 0.015)相关。SSTR3 和 SSTR4 的表达与较短的生存时间相关(P = 0.046,风险比[HR]4.703,95%CI 1.027 至 21.533;P = 0.013,HR 6.64,95%CI 1.48 至 29.64),而 SSTR1 和 SSTR2 的表达与改善的预后相关(P = 0.021,HR 0.167,95%CI 0.037 至 0.765;P = 0.022,HR 0.08,95%CI 0.01 至 0.70)。

结论

PC 中观察到 SSTR1 至 SSTR5 的表达。由于 SSTR 表达与肿瘤的转移潜能和患者预后相关,这些受体可能为个体化预后评估提供可能。

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