Table of Contents
Definition / general | Essential features | Pathophysiology | Clinical features | Interpretation | Uses by pathologists | Prognostic factors | Microscopic (histologic) description | Microscopic (histologic) images | Positive staining - normal | Positive staining - disease | Negative staining | Board review style question #1 | Board review style answer #1Cite this page: Terlević R, Vranić S. SSTR2A. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainsSSTR2A.html. Accessed January 17th, 2021.
Definition / general
- Somatostatin receptor 2a
- One of 5 members of somatostatin receptors
Essential features
- Widest expression among somatostatin receptors
- Expressed in a broad variety of neuroendocrine and other tumors
- Also expressed in normal tissues (brain, pituitary, pancreatic islet, stomach foveolar cells, duodenal glands, small and large intestine surface epithelial cells, kidney, testis, endothelium, lymphocytes, monocytes, macrophages and fibroblasts) (Exp Clin Endocrinol Diabetes 2012;120:482, Endocr J 2005;52:605)
- Expression in solid tumors generally associated with improved outcome (Pancreas 2016;45:1386, Eur J Nucl Med Mol Imaging 2017;44:468, Medicine (Baltimore) 2015;94:e1281)
Pathophysiology
- Transmembrane G protein coupled receptor widely distributed in normal human tissues
- Mediates antisecretory effects of somatostatin by inhibiting high voltage activated calcium channels (FEBS Lett 1994;355:117)
- Mediates antiproliferative effect in tumors via direct and indirect mechanisms
- Direct mechanisms include promotion of apoptosis via upregulation of Bax, inhibition of growth factor action on tumor cells via inhibition of MAPK phosphorylation and cell cycle arrest (Front Neuroendocrinol 2013;34:228)
- Indirect mechanisms include inhibition of secretion of growth factors and antiangiogenic effects via upregulation of potent angiogenic inhibitor thrombospondin-1 in pancreatic tumors, inhibition of secretion of VEGF, PDGF, IGF1 by endothelium and monocytes (Proc Natl Acad Sci U S A 2009;106:17769, Mol Endocrinol 2005;19:255)
Clinical features
- Mediates the antisecretory effect of somatostatin analogues in growth hormone secreting pituitary adenomas and hormone secreting neuroendocrine tumors of the gastrointestinal tract (Front Neuroendocrinol 2013;34:228)
Interpretation
- Membranous and cytoplasmic staining
Uses by pathologists
- Differentiates follicular dendritic cell sarcoma (positive) from inflammatory pseudotumor-like follicular dendritic cell sarcoma (negative) (Am J Surg Pathol 2019;43:374)
- Differentiates olfactory neuroblastoma (positive in 75%) from sinonasal carcinoma (negative) (Hum Pathol 2018;79:144)
- Differentiates meningioma (positive) from other mimickers including solitary fibrous tumor / hemangiopericytoma and metastatic carcinomas (Acta Neuropathol 2015;130:441, J Neuropathol Exp Neurol 2017;76:289)
Prognostic factors
- Independent predictor of improved overall survival and progression free survival in neuroendocrine tumors (NET) (Pancreas 2016;45:1386, Eur J Nucl Med Mol Imaging 2017;44:468, Medicine (Baltimore) 2015;94:e1281)
- Cytoplasmic expression correlates with increased disease free survival in neuroendocrine breast carcinoma (Oncology 2018 Oct 3 [Epub ahead of print])
- Expression correlated with better overall survival in anaplastic oligodendroglioma, IDH-mutant and 1p/19q codeleted (Acta Neuropathol Commun 2018;6:89, Oncotarget 2017;8:49123)
- Expression in medullary thyroid carcinoma correlates with improved survival, especially stage IV (Endocrine 2018;62:639)
- Improved recurrence free survival in gastrointestinal stromal tumor (Am J Transl Res 2014;6:831)
- Associated with worse prognosis in hepatocellular carcinoma (Histopathology 2017;70:492)
Microscopic (histologic) description
- Staining intensity usually variable
Positive staining - normal
- Brain, anterior pituitary, pancreatic islets, adrenal cortex (Exp Clin Endocrinol Diabetes 2012;120:482)
- Stomach and duodenum enterochromaffin cells, small and large intestine surface epithelial cells (Exp Clin Endocrinol Diabetes 2012;120:482)
- Kidney: glomerulus (Exp Clin Endocrinol Diabetes 2012;120:482)
- Testis: tubules (Exp Clin Endocrinol Diabetes 2012;120:482)
- Endothelium, lymphocytes, monocytes, macrophages and fibroblasts (Exp Clin Endocrinol Diabetes 2012;120:482)
- Follicular dendritic cells (J Cancer Res Clin Oncol 2018;144:1921)
Positive staining - disease
- Neuroendocrine tumors, particularly small intestinal (90%), pancreatic (76% - 80%) (Pancreas 2016;45:1386, Medicine (Baltimore) 2015;94:e1281)
- Neuroendocrine breast carcinoma (71%) (Ann Diagn Pathol 2019;38:62)
- Pituitary adenoma, particularly growth hormone secreting (in 65%) (Pathology 2018;50:472)
- Gastrointestinal stromal tumor (88%) (Am J Transl Res 2014;6:831)
- Olfactory neuroblastoma (75%) (Hum Pathol 2018;79:144)
- Paraganglioma (88%) (including metastases) and pheochromocytoma (73%) (Hum Pathol 2018 Dec 7 [Epub ahead of print])
- Small cell lung cancer (50%, 15 cases) (J Cancer Res Clin Oncol 2018;144:1921)
- Follicular dendritic cell sarcoma (100%) (Am J Surg Pathol 2019;43:374)
- Meningioma, including WHO grades I, II and III (J Neuropathol Exp Neurol 2017;76:289)
Negative staining
- Inflammatory pseudotumor-like follicular dendritic cell sarcoma (Hum Pathol 2018;79:144)
- Sinonasal carcinoma (Hum Pathol 2018;79:144)
Board review style question #1
- Which of the following tumors is most likely to stain with SSTR2A?
- Grade I neuroendocrine tumor of the small intestine
- Grade II neuroendocrine tumor of the pancreas
- Small cell lung cancer
- Oligodendroglioma
- Neuroendocrine breast carcinoma
Board review style answer #1