Correlation and Comparison of Somatostatin Receptor Type 2 Immunohistochemical Scoring Systems with 68Ga-DOTATATE Positron Emission Tomography/Computed Tomography Imaging in Gastroenteropancreatic Neuroendocrine Neoplasms

Abstract

Introduction: 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.

Patients and methods: 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.

Results: 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.

Conclusions: 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.

Keywords: 68Ga-DOTATATE PET/CT imaging; Gastroenteropancreatic neuroendocrine neoplasms; Immunohistochemical scoring systems; Somatostatin receptor type 2.