The Distance from Pathology to Molecular Imaging SSTR Expression Comparison in 100 Gastroenteropancreatic Neuroendocrine Neoplasms

Background: Somatostatin receptor (SSTR) overexpression is a unique feature of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs), which establish the basis for both diagnosis and therapy, including long acting somatostatin analogues and peptide receptor radionuclide therapy (PRRT). SSTR status can be evaluated by immunohistochemical staining (IHC) and 68Ga-DOTATATE PET/CT scanning.

Aim: To find the correlation between IHC and 68Ga-DOTATATE PET/CT and to explore the best cut-off value for SSTR expression.

Methods: 100 neuroendocrine tumors of 95 cases with available somatostatin receptor imaging data and pathological material were retrospectively analyzed for somatostatin receptor types 2A. According to the WHO classification (2017 edition), 100 tumors consisted of neuroendocrine tumor (NET) G1 (9 cases), NET G2 (64 cases), NET G3 (13 cases), neuroendocrine carcinoma(10 cases) and mixed neuroendocrine tumor(4 cases). The immunohistochemical results of SSTR2A were interpreted by these four well-established semi-quantitative scoring systems, including human epidermal growth factor receptor 2 (HER2)/neu score, Volante-Score, H score and immunoreactive score (IRS).

Results: In those cases without heterogeneous SSTR2A expression (about 55%), the four scoring systems were highly concordant with each other (Kendall’s Tau-b coefficient range from 0.80 to 0.99,P<0.001), and also highly correlated with 68Ga-DOTATATE PET/CT imaging (Spearman’s rank correlation was 0.71, 0.84, 0.77 and 0.71, respectively,P<0.001). Using H-score to predict the imaging results ,the AUC value was 0.99, and the sensitivity and specificity was 97.2% and 94.7% ,respectively, with a cut-off value defined as 170,which indicated 85% of tumor cells were moderately positive for SSTR2A, or 55% were strongly positive. Among those cases with heterogeneous SSTR2A expression (45%), the four scoring systems were poorly consistent with each other (Kendall Tau-b coefficient ranged from 0.40 to 0.79,P<0.01), among which IRS-score had the most inconsistency with the other three (Kendall’s Tau-b coefficient ranged from 0.41 to 0.60,P<0.01).In these cases, the correlation between IHC and 68Ga-DOTATATE PET/CT were relatively low and coefficient values of these four scoring systems were 0.53, 0.45, 0.42, and 0.37, respectively(P<0.05). The AUC value of H-score in predicting 68Ga-DOTATATE PET/CT results was 0.83, and the sensitivity and specificity were 72.5% and 77.8%, respectively, with the cut-off value as 170.

Conclusions: SSTR2 IHC can well predict 68Ga-DOTATATE results, especially in homogeneous expression group. 85% of tumor cells moderately positive or 55% strongly positive are the best reading standard for SSTR2 IHC.