Somatostatin and dopamine receptor expression in neuroendocrine neoplasms: correlation of immunohistochemical findings with somatostatin receptor scintigraphy visual scores

Diakatou, Evanthia; Alexandraki, Krystallenia Ι.; Tsolakis, Apostolos V.; Kontogeorgos, George; Chatzellis, Eleftherios; Leonti, Anastasia; Kaltsas, Gregory

doi:10.1111/cen.12775

Cited by 38 publications

(31 citation statements)

References 31 publications

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“…Our observation of a high concordance between expression SSTR2, SSTR3 and SSTR5 is consistent with prior studies. 39,40 Interestingly, we found no correlation between expression of SSTR4 and other SSTRs, suggesting that SSTR4 may play different biologic role. Previous studies have reported that high expression of SSTR2 is correlated with lower MKI67 (Ki-67) labeling index in NETs, though many of these studies included both low and high grade tumors, 22,33,38,41–44 Our study was limited to well differentiated NETs.…”

Section: Discussionmentioning

confidence: 60%

Association Between Somatostatin Receptor Expression and Clinical Outcomes in Neuroendocrine Tumors

Qian

Ter‐Minassian

et al. 2016

Pancreas

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Objective Somatostatin receptors (SSTRs), products of gene superfamily SSTR1-5, are commonly expressed in neuroendocrine tumors (NETs). Somatostatin analogs (SSAs) bind to SSTRs and are used as therapeutic agents in patients with advanced NETs. We hypothesized that tumor SSTR expression status would be associated with clinical outcomes in NET. Methods Expression of the five SSTRs was evaluated by immunohistochemistry, using tissue microarrays comprising 173 primary NETs, 24 matched metastases, and 22 metastatic NETs from 195 patients. Cox proportional hazards regression analysis was used to assess the association of SSTR expression status (high vs. low) with clinical outcomes, adjusting for potential confounders. Results High expression of SSTR2 was associated with longer overall survival in the cohort overall (multivariate hazard ratio 0.42, 95% confidence interval 0.21–0.84; P = 0.013). In a subgroup of patients with metastatic small intestine NET treated with SSAs and evaluable for progression, SSTR2 expression was associated with both longer progression-free and overall survival. No associations with progression-free or overall survival were observed with expression of other SSTRs. Conclusions Our study demonstrated that expression of SSTR2, but not other SSTRs, is associated with longer overall survival. In patients treated with SSAs, expression of SSTR2 is associated with longer progression-free survival.

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Section: Discussionmentioning

confidence: 60%

Association Between Somatostatin Receptor Expression and Clinical Outcomes in Neuroendocrine Tumors

Qian

Ter‐Minassian

et al. 2016

Pancreas

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“…The percentages of NETs that were sst 2a positive on SRS but sst 2a negative on IHC on tumor samples (sst 2a : IHC-/SRS+) varied between 0 and 15% [10,25,26]. Other sst receptor subtypes than sst 2 showed no significant relationship between IHC on tumor samples and in vivo SRS uptake on OctreoScan® [10,25,26]. Since these receptor subtypes are less frequently expressed on GEP-NETs as compared to sst 2a , we focused only on sst 2a IHC in our study [1,2,3,4].…”

Section: Discussionmentioning

confidence: 99%

Is There an Additional Value of Using Somatostatin Receptor Subtype 2a Immunohistochemistry Compared to Somatostatin Receptor Scintigraphy Uptake in Predicting Gastroenteropancreatic Neuroendocrine Tumor Response?

Adrichem¹,

Kamp²,

Deurzen³

et al. 2015

Neuroendocrinology

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Background and Aims: It is unknown whether tumoral somatostatin receptor subtype 2a (sst_2a) immunohistochemistry (IHC) has additional value compared to somatostatin receptor scintigraphy (SRS) uptake using OctreoScan® in predicting response to peptide receptor radiotherapy using ¹⁷⁷Lu-octreotate (PRRT) in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs). The aims of this study were: (1) to establish the percentage of sst_2a immunopositivity in GEP-NET samples of PRRT-treated patients, (2) to determine the relationship between best GEP-NET response using RECIST 1.0 criteria 1 year after PRRT and tumoral sst_2a IHC, and (3) to compare characteristics of patients with sst_2a IHC-negative and -positive tumors. Methods: All 73 consecutive patients were selected for PRRT based on a positive SRS. Radiological response was scored according to RECIST 1.0 criteria. sst_2a status was detected on tumor samples by IHC. Results: In total, 93% of GEP-NET samples showed sst_2a IHC positivity. No statistically significant relationship was observed between in vitro sst_2a expression and in vivo best GEP-NET response 1 year after PRRT (p = 0.47). Sex, primary tumor site, disease stage, ENETS TNM classification, Ki-67 index, highest serum chromogranin-A level, and highest neuron-specific enolase level were not significantly different between patients with negative and positive sst_2a tumoral IHC with the exception of age at diagnosis (p = 0.007). Conclusions: sst_2a IHC of tumor samples has no additional value compared to SRS uptake using OctreoScan® in predicting tumor response after PRRT.

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“…Previous studies have also evaluated the concordance between immunohistochemistry and SRS results, especially SSTR2a. These authors reported that the SSTR2a and SRS findings correlated in 82.7% of their 81 neuroendocrine neoplasms [13]. Other studies noticed that evaluation of the expression of SSTR3 and SSTR5 did not provide further concordance with the SRS findings obtained from SSTR2 expression.…”

Section: Discussionmentioning

confidence: 99%

“…SRS is clinically very useful, though few reports compare the pathologic expression of the SSTR with SRS [13]. In addition, SRS was not approved in Japan until recently.…”

Section: Introductionmentioning

confidence: 99%

Clinical Usefulness of Somatostatin Receptor Scintigraphy in Japanese Patients with Gastroenteropancreatic Neuroendocrine Tumors

Hasegawa

Kobayashi²,

Tokuhisa³

et al. 2017

Digestion

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Background/Aims: Somatostatin receptor (SSTR) scintigraphy (SRS) is the standard imaging modality for evaluation of gastroenteropancreatic neuroendocrine tumor (GEP-NET) in Western countries. However, this modality was not approved in Japan until recently. The purpose of this study was to evaluate the clinical efficacy of SRS for detecting GEP-NET in Japanese patients. Methods: Japanese patients with advanced GEP-NET were enrolled and evaluated by the SRS and CT. We also compared SRS and immunohistochemical expression of SSTR type 2a (SSTR2a). Results: We enrolled 16 patients and the primary sites were the pancreas in 9, the stomach in 1, the small intestine in 2, the colon in 3, and unknown in 1. SRS showed positive findings in 3 (100%) of grade 1 (G1) and in 12 (92.3%) of grade 2 (G2) lesions. In the liver, SRS and CT detected lesions in 13 and 14 cases, respectively. The concordance rate of SSTR2a expression with SRS findings was 93.8% in the whole body and 92.9% in the liver. Conclusions: SRS could detect almost all of G1 and G2. SRS could be useful to detect lesions, with a high concordance rate with CT and pathological findings. We confirmed that SRS is a useful and reliable modality for Japanese patients.

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Somatostatin and dopamine receptor expression in neuroendocrine neoplasms: correlation of immunohistochemical findings with somatostatin receptor scintigraphy visual scores

Abstract: Sstr2 IHC expression and SRS are useful tools for the diagnosis and management of NENs because they display a high concordance. IHC expression of DR2 seems to be of potential clinical significance in GI-NENs tumours.

Cited by 38 publications

References 31 publications

Association Between Somatostatin Receptor Expression and Clinical Outcomes in Neuroendocrine Tumors

Association Between Somatostatin Receptor Expression and Clinical Outcomes in Neuroendocrine Tumors

Is There an Additional Value of Using Somatostatin Receptor Subtype 2a Immunohistochemistry Compared to Somatostatin Receptor Scintigraphy Uptake in Predicting Gastroenteropancreatic Neuroendocrine Tumor Response?

Clinical Usefulness of Somatostatin Receptor Scintigraphy in Japanese Patients with Gastroenteropancreatic Neuroendocrine Tumors

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