Correlation of Somatostatin Receptor PET/CT Imaging Features and Immunohistochemistry in Neuroendocrine Neoplasms of the Lung: A Retrospective Observational Study

Abstract Purpose to correlate somatostatin receptor (SSTR) and proliferative activity profile (SSTR2, SSTR5, Ki-67) at immunohistochemistry (IHC) with SSTR-PET/CT imaging features in a retrospective series of lung neuroendocrine neoplasms (NEN). Proliferative activity by Ki-67 and 18F-FDG-PET/CT parameters (when available) were also correlated. Methods Among all consecutive patients who underwent SSTR-PET/CT with 68Ga-DOTA-somatostatin analogs (SSA) between July 2011 and March 2020 for lung NEN, 35 patients with a confirmed diagnosis were included. For 16 of them, 18F-FDG-PET/CT studies were available. PET/CT images were reviewed by qualitative and semi-quantitative analyses. Immunohistochemistry for SSTR2, SSTR5, and Ki-67 was assessed. An inferential analysis was performed including kappa statistic and Spearman's rank correlation test. Results Definitive diagnosis consisted of 32 low-intermediate-grade NEN (26 typical carcinoids-G1 and six atypical carcinoids-G2) and 3 high-grade NEN. Positive SSTR2-IHC was found in 63% of samples while SSTR5-IHC positivity was 17.6%. A correlation between SSTR2-IHC and SSTR-PET/CT was found in 26/35 cases (74.3%, p=0.003): 22 were concordantly positive, 4 concordantly negative. For positive IHC, 100% concordance with SSTR-PET/CT (both positive) was observed, while for negative IHC concordance (both negative) was 30.8%. In 9 cases, IHC was negative while SSTR-PET/CT was positive, even though with low-grade uptake in all but one. A significant correlation between SUVmax values at SSTR-PET/CT and the SSTR2-IHC scores was found, with low SUVmax values corresponding to negative IHC and higher SUVmax values to positive IHC (p=0.0007). When correlating 68Ga-DOTA-SSA or 18F-FDG SUVmax values with Ki-67, a significant result was found for 18F-FDG only (p=0.015). Conclusion This retrospective study showed an overall good agreement between SSTR2-IHC and tumor uptake at SSTR-PET/CT in lung NENs. SSTR-PET/CT SUVmax values can be used as a parameter of SSTR2 density. SSTR2-IHC may be proposed as surrogate of SSTR-PET/CT in selected lung NEN patients for clinical decision making when SSTR-PET/CT is not available.