Perrone Elisabetta, Treglia Giorgio, Giancipoli Romina Grazia, Leccisotti Lucia, Rindi Guido, Rufini Vittoria
Nuclear Medicine Unit, Department of Diagnostic Imaging, Oncological Radiotherapy and Hematology, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.
Faculty of Biomedical Sciences, Università della Svizzera Italiana (USI), 6900 Lugano, Switzerland.
Int J Mol Sci. 2025 Jul 8;26(14):6551. doi: 10.3390/ijms26146551.
Well-differentiated neuroendocrine neoplasms (NENs) are characterized by hyperexpression on the cell membrane of somatostatin receptors (SSTRs). The demonstration of SSTRs, mainly the subtype 2 (SSTR2), is the prerequisite for diagnostic and therapeutic strategies with radiolabeled somatostatin analogs (SSAs). SSTRs can be routinely demonstrated in vivo by SSA-positron emission tomography/computed tomography (SSA-PET/CT) and in vitro by immunohistochemistry (IHC). This systematic review and meta-analysis aimed to gather evidence from the available literature on the correlation between the in vivo PET/CT and in vitro IHC SSTR expression in NEN patients. A systematic review and meta-analysis were conducted following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) 2020 guidelines. A comprehensive literature search was performed in PubMed/MEDLINE and Cochrane Library, selecting studies correlating SSTR expression in NENs via IHC and SSA-PET/CT. Data extraction, quality assessment, and statistical analysis were performed. Eleven studies met the inclusion criteria for systematic review (345 patients). Of these, eight studies (299 patients) provided sufficient quantitative data for meta-analysis. The pooled concordance between SSA-PET/CT and IHC was 76% (95% CI: 67.7-84.2), indicating a good correlation between in vivo and in vitro SSTR2 expression. Heterogeneity among studies was moderate (I = 65%), reflecting different patient cohorts and methodologies regarding both SSA-PET/CT and IHC. No significant publication bias was detected. Our results confirmed good agreement between in vivo tumor uptake with SSA-PET/CT and in vitro SSTR2 expression with IHC, highlighting the potential of using IHC for clinical decision-making in NEN patients when SSA-PET/CT is not available.
高分化神经内分泌肿瘤（NENs）的特征是生长抑素受体（SSTRs）在细胞膜上高表达。SSTRs的显示，主要是2型亚型（SSTR2），是使用放射性标记生长抑素类似物（SSAs）进行诊断和治疗策略的前提条件。SSTRs可通过SSA-正电子发射断层扫描/计算机断层扫描（SSA-PET/CT）在体内常规显示，也可通过免疫组织化学（IHC）在体外显示。本系统评价和荟萃分析旨在从现有文献中收集关于NEN患者体内PET/CT与体外IHC SSTR表达之间相关性的证据。按照系统评价和荟萃分析的首选报告项目（PRISMA）2020指南进行了系统评价和荟萃分析。在PubMed/MEDLINE和Cochrane图书馆进行了全面的文献检索，选择通过IHC和SSA-PET/CT关联NENs中SSTR表达的研究。进行了数据提取、质量评估和统计分析。11项研究符合系统评价的纳入标准（345例患者）。其中，8项研究（299例患者）提供了足够的定量数据用于荟萃分析。SSA-PET/CT与IHC之间的合并一致性为76%（95%CI：67.7-84.2），表明体内和体外SSTR2表达之间具有良好的相关性。研究之间的异质性为中等（I² = 65%），反映了在SSA-PET/CT和IHC方面不同的患者队列和方法。未检测到显著的发表偏倚。我们的结果证实了SSA-PET/CT的体内肿瘤摄取与IHC的体外SSTR2表达之间具有良好的一致性，突出了在无法进行SSA-PET/CT时使用IHC辅助NEN患者临床决策的潜力。
