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胰腺神经内分泌肿瘤患者生长抑素受体2A免疫组化、逆转录定量聚合酶链反应及体内正电子发射断层扫描/计算机断层扫描数据的分析

Analysis of somatostatin receptor 2A immunohistochemistry, RT-qPCR, and in vivo PET/CT data in patients with pancreatic neuroendocrine neoplasm.

作者信息

Kaemmerer Daniel, Wirtz Ralph M, Fischer Elke K, Hommann Merten, Sänger Jörg, Prasad Vikas, Specht Elisa, Baum Richard P, Schulz Stefan, Lupp Amelie

机构信息

From the *Department of General and Visceral Surgery, Zentralklinik Bad Berka, Bad Berka; †STRATIFYER Molecular Pathology GmbH, Cologne; ‡Laboratory of Pathology and Cytology, Bad Berka; §Department of Nuclear Medicine, University Hospital Charité, Berlin; ∥Department of Pharmacology and Toxicology, Jena University Hospital, Friedrich Schiller University, Jena; and ¶Department of Molecular Radiotherapy and Molecular Imaging, Center for PET, Zentralklinik Bad Berka, Bad Berka, Germany.

出版信息

Pancreas. 2015 May;44(4):648-54. doi: 10.1097/MPA.0000000000000316.

DOI:10.1097/MPA.0000000000000316
PMID:25872131
Abstract

OBJECTIVE

Gallium 68 somatostatin receptor (SSTR) positron emission tomography/computed tomography (PET/CT) is one of the most sensitive imaging methods for pancreatic neuroendocrine tumors. The aim of the study was to correlate the receptor density generated from the static PET/CT (maximum standard uptake values [SUVmax], mean standard uptake values [SUVmean]) with subtype 2A SSTR (SSTR2A) immunohistochemistry and reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) gene-expression data.

METHODS

Thirty-nine tumor specimens (17 primary pancreatic tumors [PTs], 22 metastases [MTS]) of 19 patients with PET/CT scans preoperatively were evaluated. Subtype 2A SSTR expression was quantified immunohistochemically (immunoreactive score [IRS]) and on messenger RNA (mRNA) level by RT-qPCR.

RESULTS

The PT and MTS did not differ significantly in their SUVmax (P = 0.07) but displayed a dissimilarity with respect to their SSTR2A expression (mean [SD] IRS PT, 8.8 [3.6] vs mean [SD] IRS MTS, 5.1 [4.5]; P = 0.02).The SUVmean was highly significantly correlated to SSTR2A mRNA expression (C = 0.85, P < 0.001) and moderately to SSTR2A protein expression (C = 0.53, P = 0.05). Moreover, the SUVmax correlated moderately with SSTR2A protein expression (C = 0.44, P = 0.03) and mRNA expression (C = 0.64, P = 0.042).

CONCLUSIONS

The SUVmax and SUVmean are reliable ex vivo parameters for in vivo quantification of SSTR expression in pancreatic neuroendocrine tumors. Both immunohistochemistry and RT-qPCR are comparable methods for SSTR2A quantification. The PT and MTS differ significantly in their SSTR2A expression. This fact should be taken into account when treating patients with somatostatin analogs or peptide receptor radionuclide therapy.

摘要

目的

镓68生长抑素受体(SSTR)正电子发射断层扫描/计算机断层扫描(PET/CT)是胰腺神经内分泌肿瘤最敏感的成像方法之一。本研究的目的是将静态PET/CT产生的受体密度(最大标准摄取值[SUVmax]、平均标准摄取值[SUVmean])与2A亚型SSTR(SSTR2A)免疫组织化学及逆转录定量聚合酶链反应(RT-qPCR)基因表达数据相关联。

方法

对19例术前行PET/CT扫描患者的39个肿瘤标本(17个原发性胰腺肿瘤[PTs]、22个转移瘤[MTS])进行评估。通过免疫组织化学(免疫反应评分[IRS])及RT-qPCR在信使核糖核酸(mRNA)水平对2A亚型SSTR表达进行定量。

结果

PT和MTS的SUVmax无显著差异(P = 0.07),但在SSTR2A表达方面存在差异(平均[标准差]IRS PT,8.8[3.6] vs平均[标准差]IRS MTS,5.1[4.5];P = 0.02)。SUVmean与SSTR2A mRNA表达高度显著相关(C = 0.85,P < 0.001),与SSTR2A蛋白表达中度相关(C = 0.53,P = 0.05)。此外,SUVmax与SSTR2A蛋白表达中度相关(C = 0.44,P = 0.03),与mRNA表达中度相关(C = 0.64,P = 0.042)。

结论

SUVmax和SUVmean是胰腺神经内分泌肿瘤体内SSTR表达体外定量的可靠参数。免疫组织化学和RT-qPCR都是SSTR2A定量的可比方法。PT和MTS在SSTR2A表达上有显著差异。在使用生长抑素类似物或肽受体放射性核素治疗患者时应考虑这一事实。

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