SSTR2A Protein Expression in Neuroendocrine Neoplasms of the Colorectum
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Background: Expression studies of somatostatin receptor type 2A (SSTR2A) in neuroendocrine neoplasms (NENs) led to the development of clinically relevant diagnostic and therapeutic strategies. However, most of these strategies used in-house-developed antibodies and were focused on lung tumors. We evaluated commercially available SSTR2A antibodies in NENs of the colorectum to observe their subcellular localization and distribution within the resected tumor. Methods: The immunohistochemistry of 77 NENs located in the colorectum were studied using a commercially available antibody against SSTR2A. Results: Most neuroendocrine tumors (NET) grade (G)1 and G2 expressed the SSTR2A in the cytoplasm with apical or luminal localization. However, all neuroendocrine carcinomas (NEC) G3 were negative for SSTR2A. Conclusions: Our data indicate that SSTR2A immunohistochemistry shows cytoplasmic staining with distinct subcellular localization in most NET G1 in the colorectum using a commercially available antibody. Low or no expression of SSTR2A in NET G2 and NEC G3 raises the possibility that SSTR2A may correlate with histologic differentiation and proliferative activity. Further validation studies in large case series are needed.
Abstract
Background: Expression studies of somatostatin receptor type 2A (SSTR2A) in neuroendocrine neoplasms (NENs) led to the development of clinically relevant diagnostic and therapeutic strategies. However, most of these strategies used in-house-developed antibodies and were focused on lung tumors. We evaluated commercially available SSTR2A antibodies in NENs of the colorectum to observe their subcellular localization and distribution within the resected tumor. Methods: The immunohistochemistry of 77 NENs located in the colorectum were studied using a commercially available antibody against SSTR2A. Results: Most neuroendocrine tumors (NET) grade (G)1 and G2 expressed the SSTR2A in the cytoplasm with apical or luminal localization. However, all neuroendocrine carcinomas (NEC) G3 were negative for SSTR2A. Conclusions: Our data indicate that SSTR2A immunohistochemistry shows cytoplasmic staining with distinct subcellular localization in most NET G1 in the colorectum using a commercially available antibody. Low or no expression of SSTR2A in NET G2 and NEC G3 raises the possibility that SSTR2A may correlate with histologic differentiation and proliferative activity. Further validation studies in large case series are needed.
참고문헌 (20)
- Li Y, "Rheumatic valvular surgery and concomitant radiofrequency Maze procedure: TGF-beta1 mRNA expression predicting the efficacy", Zhonghua Wai Ke Za Zhi, 48, pp.820~824 (2010)
- Volante M, "Somatostatin receptor type 2A immunohistochemistry in neuroendocrine tumors: a proposal of scoring system correlated with somatostatin receptor scintigraphy", Mod Pathol, 20, pp.1172~1182 (2007)
- Bosman FT, "WHO classification of tumours of the digestive system. 4th ed" (2010), IARC Press
- Edge SB, "AJCC cancer staging manual. 7th ed" (2010), Springer
- Volante M, "Somatostatin receptors and their interest in diagnostic pathology", Endocr Pathol, 15, pp.275~291 (2004)
- Patel YC, "Subtype selectivity of peptide analogs for all five cloned human somatostatin receptors (hsstr 1-5)", Endocrinology, 135, pp.2814~2817 (1994)
- Reubi JC, "Concomitant expression of several peptide receptors in neuroendocrine tumours: molecular basis for in vivo multireceptor tumour targeting", Eur J Nucl Med Mol Imaging, 30, pp.781~793 (2003)
- Reubi JC, "Detection of somatostatin receptors in surgical and percutaneous needle biopsy samples of carcinoids and islet cell carcinomas", Cancer Res, 50, pp.5969~5977 (1990)
- Körner M, "Value of immunohistochemistry for somatostatin receptor subtype sst2A in cancer tissues: lessons from the comparison of anti-sst2A antibodies with somatostatin receptor autoradiography", Am J Surg Pathol, 29, pp.1642~1651 (2005)
- Bruns C, "Molecular pharmacology of somatostatin-receptor subtypes", Ann N Y Acad Sci, 733, pp.138~146 (1994)
- Kulaksiz H, "Identification of somatostatin receptor subtypes 1, 2A, 3, and 5 in neuroendocrine tumours with subtype specific antibodies", Gut, 50, pp.52~60 (2002)
- Kang GH, "DOG1 and PKC-theta are useful in the diagnosis of KIT-negative gastrointestinal stromal tumors", Mod Pathol, 24, pp.866~875 (2011)
- Reubi JC, "Somatostatin receptors in human cancer: incidence, characteristics, functional correlates and clinical implications", J Steroid Biochem Mol Biol, 43, pp.27~35 (1992)
- Lamberts SW, "The role of somatostatin and its analogs in the diagnosis and treatment of tumors", Endocr Rev, 12, pp.450~482 (1991)
- Janson ET, "Determination of somatostatin receptor subtype 2 in carcinoid tumors by immunohistochemical investigation with somatostatin receptor subtype 2 antibodies", Cancer Res, 58, pp.2375~2378 (1998)
- Liu Q, "Receptor signaling and endocytosis are differentially regulated by somatostatin analogs", Mol Pharmacol, 68, pp.90~101 (2005)
- Csaba Z, "In vivo internalization of the somatostatin sst2A receptor in rat brain: evidence for translocation of cell-surface receptors into the endosomal recycling pathway", Mol Cell Neurosci, 17, pp.646~661 (2001)
- Liu Q, "In vivo phosphorylation of the somatostatin 2A receptor in human tumors", J Clin Endocrinol Metab, 88, pp.6073~6079 (2003)
- Reubi JC, "Somatostatin (SRIH) messenger ribonucleic acid expression in human neuroendocrine and brain tumors using in situ hybridization histochemistry: comparison with SRIH receptor content", J Clin Endocrinol Metab, 76, pp.642~647 (1993)
- Papotti M, "Expression of somatostatin receptor types 1-5 in 81 cases of gastrointestinal and pancreatic endocrine tumors: a correlative immunohistochemical and reverse-transcriptase polymerase chain reaction analysis", Virchows Arch, 440, pp.461~475 (2002)
