Correlation of somatostatin receptor PET/CT imaging features and immunohistochemistry in neuroendocrine tumors 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 tumors (NET). Proliferative activity by Ki-67 and ¹⁸F-FDG-PET/CT parameters (when available) were also correlated.

Methods: Among 551 patients who underwent SSTR-PET/CT with ⁶⁸Ga-DOTA-somatostatin analogs (SSA) between July 2011 and March 2020 for lung neuroendocrine neoplasms, 32 patients with a confirmed diagnosis of NET were included. For 14 of them, ¹⁸F-FDG-PET/CT was available. PET/CT images were reviewed by qualitative and semi-quantitative analyses. Immunohistochemistry for SSTR2, SSTR5, and Ki-67 was assessed. Inferential analysis was performed including kappa statistics and Spearman's rank correlation test.

Results: Definitive diagnosis consisted of 26 typical carcinoids-G1 and six atypical carcinoids-G2. Positive SSTR2-IHC was found in 62.5% of samples while SSTR5-IHC positivity was 19.4%. A correlation between SSTR2-IHC and SSTR-PET/CT was found in 24/32 cases (75.0%, p = 0.003): 20 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 33.3%. In 8 cases, IHC was negative while SSTR-PET/CT was positive, even though with low-grade uptake in all but one. A significant correlation between SUV_max values at SSTR-PET/CT and the SSTR2-IHC scores was found, with low SUV_max values corresponding to negative IHC and higher SUV_max values to positive IHC (p = 0.002).

Conclusion: This retrospective study showed an overall good agreement between SSTR2-IHC and tumor uptake at SSTR-PET/CT in lung NETs. SSTR-PET/CT SUV_max values can be used as a parameter of SSTR2 density. Within the limits imposed by the relatively small cohort, our data suggest that SSTR2-IHC may surrogate SSTR-PET/CT in selected lung NET patients for clinical decision making when SSTR-PET/CT is not available.

Keywords: Immunohistochemistry; Ki-67; Lung NET; PET/CT; Somatostatin receptor subtypes; [68Ga]-DOTA-somatostatin analogs.

Fig. 1

The flowchart of study population

Fig. 2

Concordant and discordant findings of pathological and functional assessments with representative images of SSTR2-IHC and SSTR-PET/CT (fused transaxial images) corresponding to the various IHC scores and Krenning scores (KS), respectively; arrows indicate lung lesions. A Patients with negative SSTR2-IHC (score 0 and 1) and B patients with positive SSTR2-IHC (score 2 and 3)

Fig. 3

A Box plot of SSTR-PET/CT SUV_max by SSTR2-IHC scores ranging from 0 to 3. The boxes indicate medians with upper (Q3) and lower quartiles (Q1); the upper and lower bars define values between Q3 − Q3 + 3/2(Q3 − Q1) and Q1–3/2(Q3 − Q1) − Q1, respectively; dots indicate outliers. p value was evaluated with two-sided Kruskal–Wallis test. B Correlation between SSTR-PET/CT SUV_max (blue dots) and ¹⁸F-FDG-PET/CT SUV_max (red crosses) and proliferation index Ki-67 in the overall series. Coefficients of correlation (rho) and p values were calculated with two-sided Spearman’s rank correlation test

Fig. 4

Correlation between SSTR/PET/CT SUV_max (blue dots) and ¹⁸F-FDG-PET/CT SUV_max (red crosses) and proliferation index Ki-67 in typical carcinoids (TC/NET-G1) (A) and atypical carcinoids (AC/NET-G2) (B). Coefficients of correlation (rho) and p values were calculated with two-sided Spearman’s rank correlation test