ORIGINAL ARTICLE
Evaluation of the expression of somatostatin receptors by immunohistochemistry in neuroendocrine tumors of the small intestine
1
Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, Poznan, Poland
2
Department of Pharmacology, Poznan University of Medical Sciences, Poznan, Poland
3
Department of Clinical Pathology, Poznan University of Medical Sciences, Poznan, Poland
4
Provincial Integrated Hospital L. Perzyny, Kalisz, Poland
Submission date: 2019-06-03
Final revision date: 2020-01-26
Acceptance date: 2020-03-08
Publication date: 2020-05-20
Pol J Pathol 2020;71(1):30-37
KEYWORDS
TOPICS
ABSTRACT
Most neuroendocrine neoplasms (NEN) are characterized by the presence of somatostatin receptors (SSTR) which we use in location diagnostics and treatment. The aim of this study was to evaluate the expression of somatostatin receptors by immunohistochemistry in tissue obtained after surgery of the primary focus in the small intestine.
The group of patients consisted of 41 people, in 18 cases the primary tumor was in the jejunum and in 23 in the ileum. The immunohistochemical method was used to visualize the receptors, using polyclonal antibodies in a two-stage peroxidase method.
In patients with NEN of the small intestine, the SSTR2a and SSTR5 receptors are most commonly expressed, followed by SSTR2b and 3. In statistical analysis, it was shown that the expression of somatostatin receptors was not dependent on the primary site of the tumor (p > 0.05). The dependence of SSTR expression on histological maturity is evident. SSTR1, SSTR2b, SSTR3 and SSTR5 are more common in tumors with grading G1 (p < 0.05). In the study group, the exception was SSTR2a, whose incidence was comparable in both groups (p = 0.35).
In NEN of the small intestine, the expression SSTR2a and SSTR5 is the most common.
The group of patients consisted of 41 people, in 18 cases the primary tumor was in the jejunum and in 23 in the ileum. The immunohistochemical method was used to visualize the receptors, using polyclonal antibodies in a two-stage peroxidase method.
In patients with NEN of the small intestine, the SSTR2a and SSTR5 receptors are most commonly expressed, followed by SSTR2b and 3. In statistical analysis, it was shown that the expression of somatostatin receptors was not dependent on the primary site of the tumor (p > 0.05). The dependence of SSTR expression on histological maturity is evident. SSTR1, SSTR2b, SSTR3 and SSTR5 are more common in tumors with grading G1 (p < 0.05). In the study group, the exception was SSTR2a, whose incidence was comparable in both groups (p = 0.35).
In NEN of the small intestine, the expression SSTR2a and SSTR5 is the most common.
REFERENCES (39)
1.
Woltering EA, Bergsland EK, Beyer DT, et al. Neuroendocrine Tumors of the Stomach. American Joint Committee on Cancer 2017. In: Amin MB, et al (eds.) AJCC Cancer Staging Manual. Eight Edition. Springer 2017; 351-359.
2.
Basturk O, Yang Z, Tang LH, et al. The high-grade (WHO G3) pancreatic neuroendocrine tumor category is morphologically and biologically heterogenous and includes both well differentiated and poorly differentiated neoplasms. Am J Surg Pathol 2015; 39: 683-690.
3.
Burke AP, Thomas RM, Elasyed AM. Carcinoid of the jejunum and ileum-an immunohistochemical and clinicopathological study of 167 cases. Cancer 1997; 79: 1086-1093.
4.
Monson JP. The epidemiology of endocrine tumors. Endocr Relat Cancer 2000; 7: 29-36.
5.
Modlin IM, Kidd M, Latich I. Current status of gastrointestinal carcinoids. Gastroenterology 2005; 128: 1717-1751.
6.
Gut P, Waligórska-Stachura J, Czarnywojtek A, et al. Hindgut neuroendocrine neoplasms – characteristics and prognosis. Arch Med Sci 2017; 13: 1427-1432.
7.
Eriksson B, Kloppel G, Krenning G. Consensus guidelines for the management of patients with digestive neuroendocrine tumors – well differentiated jejunal-ileal tumor/carcinoma. Neuroendocrinology 2008; 87: 8-19.
8.
Modlin IM, Lye KD, Kidd M. A 5-decade analysis of 13,715 carcinoid tumors. Cancer 2003; 97: 934-959.
9.
Yalcin S, Bayram F, Erdamar S, et al. Gastroenteropancreatic neuroendocrine tumors: recommendations of Turkish multidisciplinary neuroendocrine tumor study group on diagnosis, treatment and follow-up. Arch Med Sci 2017; 13: 271-282.
10.
Florio T, Rim C, Hershberger RE, et al. The somatostatin receptor SSTR1 is coupled to phosphotyrosine phosphatase activity in CHO-K1 cells. Mol Endocrinol 1994; 8: 1289-1297.
11.
Reardon DB, Wood SL, Brautigan DL, et al. Activation of a protein tyrosine phosphatase and inactivation of Raf-1 by somatostatin. Biochem J 1996; 314: 401-404.
12.
Sharma K, Patel YC, Srikant CB. C-terminal region of human somatostatin receptor 5 is required for induction of Rb and G1 cell cycle arrest. Mol Endocrinol 1999; 13: 82-90.
13.
Sharma K, Patel YC, Srikant CB. Subtype-selective induction of wild-type p53 and apoptosis, but not cell cycle arrest, by human somatostatin receptor 3. Mol Endocrinol 1996; 10: 1688-1696.
14.
Duran Prado N, Gahete MD, Martinez Fuentes AJ. Identification and characterization of two novel truncated but functional isoforms of the somatostatin receptor subtype 5 differentially present in pituitary tumors. J Clin Endocrinol Metab 2009; 94: 2634-2643.
15.
Kunikowska J, Pawlak D, B¹k MI, et al. Long-term results and tolerability of tandem peptide receptor radionuclide therapy with 90Y/177Lu-DOTATATE in neuroendocrine tumors with respect to the primary location: a 10-year study. Ann Nucl Med 2017; 31: 347-356.
16.
Pawlikowski M, Pisarek H, Kunert Radek J. Somatostatin receptors in GH-secreting pituitary adenomas- their relationship to the response to octreotide. Endokrynol Pol 2008; 59: 196-199.
17.
Culler MD, Pawlikowski M. Somatostatin analogs: lessons in functional complexity and receptor interactions. Landes Bioscience Austin 2007: 21-37.
18.
Kos-Kud³a B, Blicharz-Dorniak J, Strzelczyk J, et al. Diagnostic and therapeutic guidelines for gastro-entero-pancreatic neuroendocrine neoplasms (recommended by the Polish Network of Neuroendocrine Tumors). Endokrynol Pol 2017; 68: 79-110.
19.
Pisarek H, Stepieñ T, Kubiak R, et al. Expression of somatostatin receptor subtypes in human thyroid tumors: the immunohistochemical and molecular biology (RT-PCR) investigation. Thyroid Res. 2009; 2: 10-16.
20.
Papotti M, Bongiovanni M, Volante M, et al. 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 2002; 440: 461-475.
21.
Corleto VD, Falconi M, Panzuto F, et al. Somatostatin receptor subtypes 2 and 5 are associated with better survival in well-differentiated endocrine carcinomas. Neuroendocrinology 2009; 89: 223-230.
22.
Mehta S, de Reuver PR, Gill P, et al. Somatostatin Receptor SSTR-2a Expression Is a Stronger Predictor for Survival Than Ki-67 in Pancreatic Neuroendocrine Tumors. Medicine (Baltimore) 2015; 94: 1281-1287.
23.
Hubalewska-Dydejczyk A, Trofimiuk M, Szybiñski P, et al. Somatostatin receptors expression in pancreatic GEP-NET tumors-preliminary results. 5th Annual ENETS Conference. 2008; abstr B14.
24.
Reubi JC, Waser B, Liu Q, et al. Subcellular distribution of somatostatin sstr2A receptors in human tumors of the nervous and neuroendocrine systems, membranous versus intracellular location. J Clin Endocrinol Metab 2000; 85: 3882-3891.
25.
Kaemmerer D, Peter L, Lupp A, et al. Comparing of IRS and Her2 as immunohistochemical scoring schemes in gastroenteropancreatic neuroendocrine tumors. Int J Clin Exp Pathol 2012; 5: 187-194.
26.
Fjällskog ML, Ludvigsen E, Stridsberg M, et al. Expression of somatostatin receptor subtypes 1 to 5 in tumor tissue and intratumoral vessels in malignant endocrine pancreatic tumors. Med Oncol 2003; 20: 59-67.
27.
Kulaksiz H, Eissele R, Rössler D, et al. Identification of somatostatin receptor subtypes 1, 2A, 3, and 5 in neuroendocrine tumors with subtype specific antibodies. Gut 2002; 50: 52-60.
28.
Diakatou E, Kaltsas G, Tzivras M, et al. Somatostatin and dopamine receptor profile of gastroenteropancreatic neuroendocrine tumors: an immunohistochemical study. Endocr Pathol 2011; 22: 24-30.
29.
Mizutani G, Nakanishi Y, Watanabe N, et al. Expression of Somatostatin Receptor (SSTR) Subtypes (SSTR-1, 2A, 3, 4 and 5) in Neuroendocrine Tumors Using Real-time RT-PCR Method and Immunohistochemistry. Acta Histochem Cytochem 2012; 45: 167-176.
30.
Zamora V, Cabanne A, Salanova R, et al. Immunohistochemical expression of somatostatin receptors in digestive endocrine tumors. Dig Liver Dis 2010; 42: 220-225.
31.
Volante M, Brizzi MP, Faggiano A, et al. Somatostatin receptor type 2A immunohistochemistry in neuroendocrine tumors: a proposal of scoring system correlated with somatostatin receptor scintigraphy. Mod Pathol 2007; 20: 1172-1182.
32.
Kim HS, Lee HS, Kim WH, et al. Clinical significance of protein expression of cyclooxygenase-2 and somatostatin receptors in gastroenteropancreatic neuroendocrine tumors. Cancer Res Treat 2011; 43: 181-188.
33.
Yerci O, Sehitoglu I, Ugras N, et al. Somatostatin receptor 2 and 5 expressions in gastroenteropancreatic neuroendocrine tumors in Turkey. Asian Pac J Cancer Prev 2015; 16: 4377-4381.
34.
Kaemmerer D, Athelogou M, Lupp A, et al. Somatostatin receptor immunohistochemistry in neuroendocrine tumors: comparison between manual and automated evaluation. Int J Clin Exp Pathol 2014; 7: 4971-4980.
35.
Gatto F, Barbieri F, Arvigo M, et al. Biological and biochemical basis of the differential efficacy of first and second generation somatostatin receptor ligands in neuroendocrine neoplasms. Int J Mol Sci 2019; 20: 3940.
36.
Saif MW, Parikh R, Ray D, et al. Medical record review of transition to lanreotide following octreotide for neuroendocrine tumors. J Gastrointest Oncol 2019; 10: 674-687.
37.
Ryan P, McBride A, Ray D, Pulgar S, et al. Lanreotide vs octreotide LAR for patients with advanced gastroenteropancreatic neuroendocrine tumors: An observational time and motion analysis. J Oncol Pharm Pract 2019; 25: 1425-1433.
38.
Brominska B, Gabryel P, Jarmo³owska-Jurczyszyn D, et al. Clinical significance of nestin and its association with survival in neuroendocrine lung tumours. Pol J Pathol 2017; 68: 291-296.
39.
Simtniece Z, Vanags A, Strumfa I, et al. Morphological and immunohistochemical profile of pancreatic neuroendocrine neoplasms. Pol J Pathol 2015; 66: 176-194.
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