Somatostatin receptor type 2A immunohistochemistry in neuroendocrine tumors: a proposal of scoring system correlated with somatostatin receptor scintigraphy

Abstract

Typing somatostatin receptor expression in neuroendocrine tumors is of relevance to target somatostatin analogue-based diagnostic approach and treatment. The expanding use of immunohistochemistry to detect somatostatin receptors is to date not paralleled by an accurate methodological setting and standardized interpretation of the results. A multicentric study was designed to compare somatostatin receptor immunohistochemical expression with in vivo scintigraphic data and verify its usefulness in the clinical management of neuroendocrine tumors. After methodological setting by testing different somatostatin receptor antibodies, 107 cases of neuroendocrine tumors with available somatostatin receptor scintigraphy data and pathological material were retrospectively analyzed for somatostatin receptor types 2A, 3 and 5 immunohistochemical expression, and compared with scintigraphic images and, whenever available, with the clinical response to somatostatin analogue treatment. Restricting 'positive cases' to the presence of a membrane pattern of staining, an overall somatostatin receptor type 2A immunohistochemistry/somatostatin receptor scintigraphy agreement of 77% (v 2 test Po0.0001) was reached. Lower concordance ratios were detected in preoperative and metastatic tumor samples, possibly as a consequence of somatostatin receptor expression heterogeneity. Pure somatostatin receptor type 2A cytoplasmic staining showed poor correlation with somatostatin receptor scintigraphy (54% concordance rate). The immunohistochemical detection of somatostatin receptor types 3 and 5, which showed almost exclusively a cytoplasmic pattern, did not improve the concordance with scintigraphic data. In a pilot series, somatostatin receptor type 2A immunohistochemistry correlated with clinical response in 75% of cases. In conclusion, we propose a scoring system for somatostatin receptor type 2A immunohistochemistry in neuroendocrine tumors correlated with in vivo data, based on the evidence that only membrane (rather that cytoplasmic) staining should be considered for a reliable, standardized and clinically relevant report.

Olfactory receptor 51E1 as a novel target for diagnosis in somatostatin receptor-negative lung carcinoids

“…For the OR51E1 receptor, the relevance of membrane localization to diagnosis of NETs is heralded by the use of other G-protein-coupled receptors, e.g. SSTRs, as mainly membrane rather than cytoplasmic immunoreactivity should be considered for a standardized and reliable clinical report (Volante et al 2007). In our study, OR51E1 has shown more extensive membrane localization compared with SSTR2, SSTR3, and SSTR5, which are targeted by most of the clinically available SSAs.…”

“…Immunohistochemical results for the relevant antibodies were rendered semiquantitatively on a scale from 0 to 3, taking into account the cellular compartmentalization (membrane vs cytoplasm) and the percentage of tumor cells (!50 vs O50%), which slightly modifies a previously released scoring system for SSTR2 (Volante et al 2007). Briefly, pure cytoplasmic immunoreactivity in !50% tumor cells and/or membrane immunoreactivity (partial or circumferential) in !10% tumor cells was scored as 0 (S0) (this modification was done in agreement with autoradiography results (Korner et al 2012)); pure cytoplasmic immunoreactivity in O50% tumor cells as 1 (S1); incomplete membranous immunoreactivity (!50% of cell circumference) in 10-50% tumor cells, irrespective of the presence of cytoplasmic immunoreactivity, as 2 (S2); and circumferential membranous immunoreactivity (R50% of cell circumference) in O50% tumor cells, irrespective of the presence of cytoplasmic immunoreactivity, as 3 (S3).…”

Factors predicting pasireotide responsiveness in somatotroph pituitary adenomas resistant to first-generation somatostatin analogues: an immunohistochemical study

“…A standardized scoring system could facilitate the routine evaluation of SSTR expression of somatotroph adenomas and would help to provide straightforward information for the clinicians. The scoring system we have used takes into account both the subcellular localization and the extent of the staining, and has been shown to represent a clinically meaningful parameter in neuroendocrine tumours (33,42). Based on our data, we propose that this could be extended to pituitary adenomas as well.…”

“…SSTR expression was scored as previously proposed by Volante et al (33), taking into account both the subcellular localization and the extent of the staining: score 0, no immunoreactivity; score 1, cytoplasmic immunoreactivity; score 2, membranous staining in !50% of cells or incomplete membranous staining; score 3, circumferential membranous staining in more than 50% of tumour cells.…”

99mTc-EDDA/HYNIC-TOC in management of patients with head and neck somatostatin receptor positive tumors

“…Somatostatin scintigraphy of receptors type 2 with radiolabeled octreotide has been shown to be very useful in the meningioma diagnosis [21][22][23]. In their published study Wang et al showed that 99m Tc-HYNIC-octreotide SPECT/CT SRS is a sensitive method for detecting meningioma [24].…”