Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing, China.
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pathology, Peking University Cancer Hospital & Institute, Beijing, China,
Neuroendocrinology. 2022;112(4):358-369. doi: 10.1159/000517530. Epub 2021 Jun 2.
The overexpression of somatostatin receptor type 2 (SSTR2) is a unique characteristic of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs), which establishes the basis for both diagnosis and therapy. The SSTR status can be evaluated by immunohistochemical staining (IHC) and 68Ga-DOTATATE positron emission tomography/computed tomography (PET/CT) imaging. This study attempted to determine the relationship between IHC and 68Ga-DOTATATE PET/CT imaging and to explore the optimal cutoff value for SSTR IHC reading.
A total of 100 GEP-NENs with SSTR PET/CT and pathological data were retrospectively analyzed, which consisted of neuroendocrine tumor (NET) G1 (n = 9), NET G2 (n = 64), NET G3 (n = 13), neuroendocrine carcinoma ( n = 10), and mixed neuroendocrine-non-NENs ( n = 4). SSTR2-IHC results were interpreted by 4 well-established semiquantitative scoring systems, including human epidermal growth factor receptor 2 (HER2) score, Volante score, H score, and immunoreactive score.
In the homogeneous SSTR2 expression group (accounting for 57% of all cases), the 4 scoring systems were highly concordant with each other (Kendall's Tau-b coefficient range: 0.80-0.96, p < 0.001) and also highly correlated with the 68Ga-DOTATATE PET/CT imaging results (Spearman's rank correlation coefficients: 0.71, 0.86, 0.80, and 0.71, p < 0.001). In the heterogeneous group (43%), the 4 scoring systems revealed a lower level of concordance (the Kendall Tau-b coefficient range: 0.40-0.75, p < 0.01), and the correlation with 68Ga-DOTATATE PET/CT imaging was also lower, albeit statistically significant (Spearman's rank correlation coefficients: 0.53, 0.38, 0.36, and 0.33, p < 0.05). Heterogeneous SSTR2 expression was mainly observed in the HER2 2+ cases, for which the combination with H score could help identify positive cases with increased sensitivity and specificity. The highest sensitivity and specificity of H scores in predicting the imaging results were achieved at 86.10 and 89.30% when defining the cutoff value as 160, indicating that 80% of the tumor cells were moderately positive or 55% were strongly positive.
SSTR2 IHC was found to predict 68Ga-DOTATATE PET/CT imaging accurately, especially in the homogeneous expression group. According to the positive 68Ga-DOTATATE PET/CT outcomes, 80% of the tumor cells moderately positive or 55% strongly positive was the cutoff values for SSTR2-IHC reading.
生长抑素受体 2 型（SSTR2）的过度表达是胃肠胰神经内分泌肿瘤（GEP-NENs）的独特特征，为诊断和治疗奠定了基础。SSTR 状态可以通过免疫组织化学染色（IHC）和 68Ga-DOTATATE 正电子发射断层扫描/计算机断层扫描（PET/CT）成像来评估。本研究试图确定 IHC 与 68Ga-DOTATATE PET/CT 成像之间的关系，并探讨 SSTR IHC 读数的最佳截断值。
回顾性分析了 100 例具有 SSTR PET/CT 和病理数据的 GEP-NENs，其中包括神经内分泌肿瘤（NET）G1（n=9）、NET G2（n=64）、NET G3（n=13）、神经内分泌癌（n=10）和混合神经内分泌-非神经内胚层肿瘤（n=4）。通过 4 种成熟的半定量评分系统（包括人表皮生长因子受体 2（HER2）评分、Volante 评分、H 评分和免疫反应评分）来解释 SSTR2-IHC 结果。
在同质 SSTR2 表达组（占所有病例的 57%）中，4 种评分系统彼此高度一致（Kendall's Tau-b 系数范围：0.80-0.96，p<0.001），并且与 68Ga-DOTATATE PET/CT 成像结果也高度相关（Spearman 秩相关系数：0.71、0.86、0.80 和 0.71，p<0.001）。在异质组（43%）中，4 种评分系统显示出较低的一致性（Kendall Tau-b 系数范围：0.40-0.75，p<0.01），与 68Ga-DOTATATE PET/CT 成像的相关性也较低，但具有统计学意义（Spearman 秩相关系数：0.53、0.38、0.36 和 0.33，p<0.05）。SSTR2 异质表达主要见于 HER2 2+ 病例，其中与 H 评分的结合有助于提高敏感性和特异性来识别阳性病例。当定义截值为 160 时，H 评分在预测成像结果方面的最高敏感性和特异性分别为 86.10%和 89.30%，表明 80%的肿瘤细胞呈中度阳性或 55%呈强阳性。
SSTR2 IHC 被发现可准确预测 68Ga-DOTATATE PET/CT 成像，特别是在同质表达组。根据阳性 68Ga-DOTATATE PET/CT 结果，SSTR2-IHC 读数的截断值为 80%的肿瘤细胞中度阳性或 55%的肿瘤细胞强阳性。
