Somatostatin Receptor 2 (SSTR2) Expression is Associated with Better Clinical Outcome and Prognosis in Rectal Neuroendocrine Tumors

Overview

Journal Sci Rep

Specialty Science

Date 2024 Feb 19

PMID 38374188

Authors

Joo Young Kim

Jisup Kim

Yong-Il Kim

Dong-Hoon Yang

Changhoon Yoo

In Ja Park

Baek-Yeol Ryoo

Jin-Sook Ryu

Seung-Mo Hong

Affiliations

Soon will be listed here.

Abstract

Somatostatin analogues have recently been used as therapeutic targets for metastatic or surgically unresectable gastroenteropancreatic (GEP) neuroendocrine tumors (NETs), and associated somatostatin receptor (SSTR) expression has been well demonstrated in most GEP NETs, with the exception of rectal NETs. SSTR2 immunohistochemical expressions were evaluated in 350 surgically or endoscopically resected rectal NETs and compared to clinicopathologic factors. SSTR2 expression was observed in 234 (66.9%) rectal NET cases and associated tumors with smaller size (p = 0.001), low pT classification (p = 0.030), low AJCC tumor stage (p = 0.012), and absence of chromogranin expression (p = 0.009). Patients with rectal NET and SSTR2 expression had significantly better overall survival than those without SSTR2 expression both by univariable (p = 0.006) and multivariable (p = 0.014) analyses. In summary, approximately two-thirds of rectal NETs expressed SSTR2. SSTR2 expression was significantly associated with favorable behavior and good overall survival in patients with rectal NETs. Furthermore, SSTR2 expression can be used as prognostic factors. When metastatic disease occurs, SSTR2 expression can be used a possible target for somatostatin analogues.

Citing Articles

GATIS score: An innovative prognostic score for rectal neuroendocrine neoplasms.

Paramythiotis D, Tsavdaris D, Karlafti E World J Gastroenterol. 2025; 31(6):100458.

PMID: 39958453 PMC: 11752696. DOI: 10.3748/wjg.v31.i6.100458.

Pancreatic endocrine and exocrine signaling and crosstalk in physiological and pathological status.

Hu C, Chen Y, Yin X, Xu R, Yin C, Wang C Signal Transduct Target Ther. 2025; 10(1):39.

PMID: 39948335 PMC: 11825823. DOI: 10.1038/s41392-024-02098-3.

User-friendly prognostic model for rectal neuroendocrine tumours: In the era of precision management.

Chen S, Xie C World J Gastroenterol. 2024; 30(45):4850-4854.

PMID: 39649545 PMC: 11606373. DOI: 10.3748/wjg.v30.i45.4850.

Preclinical safety and effectiveness of a long-acting somatostatin analogue [Ac]Ac-EBTATE against small cell lung cancer and pancreatic neuroendocrine tumors.

Njotu F, Pougoue Ketchemen J, Babeker H, Henning N, Tikum A, Nwangele E Eur J Nucl Med Mol Imaging. 2024; 52(4):1305-1320.

PMID: 39627348 DOI: 10.1007/s00259-024-07011-2.

An Update on the Management of Rectal Neuroendocrine Neoplasms.

Frydman A, Srirajaskanthan R Curr Treat Options Oncol. 2024; 25(11):1461-1470.

PMID: 39476215 PMC: 11541365. DOI: 10.1007/s11864-024-01267-4.

References

Cho M, Kim J, Sohn J, Kim M, Kim K, Kim W . Current Trends of the Incidence and Pathological Diagnosis of Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs) in Korea 2000-2009: Multicenter Study. Cancer Res Treat. 2012; 44(3):157-65. PMC: 3467418. DOI: 10.4143/crt.2012.44.3.157. View

Tsai H, Wu C, Tsai C, Lin S, Chen L, Chang J . The epidemiology of neuroendocrine tumors in Taiwan: a nation-wide cancer registry-based study. PLoS One. 2013; 8(4):e62487. PMC: 3632554. DOI: 10.1371/journal.pone.0062487. View

Fraenkel M, Kim M, Faggiano A, de Herder W, Valk G . Incidence of gastroenteropancreatic neuroendocrine tumours: a systematic review of the literature. Endocr Relat Cancer. 2013; 21(3):R153-63. DOI: 10.1530/ERC-13-0125. View

Kim J, Kim K, Kim K, Park I, Lee J, Myung S . Non-L-cell immunophenotype and large tumor size in rectal neuroendocrine tumors are associated with aggressive clinical behavior and worse prognosis. Am J Surg Pathol. 2015; 39(5):632-43. DOI: 10.1097/PAS.0000000000000400. View

Lee S, Kim B, Chang H, Sohn D, Han K, Hong C . Rectal neuroendocrine and L-cell tumors: diagnostic dilemma and therapeutic strategy. Am J Surg Pathol. 2013; 37(7):1044-52. DOI: 10.1097/PAS.0b013e3182819f0f. View

Filopanti M, Ronchi C, Ballare E, Bondioni S, Lania A, Losa M . Analysis of somatostatin receptors 2 and 5 polymorphisms in patients with acromegaly. J Clin Endocrinol Metab. 2005; 90(8):4824-8. DOI: 10.1210/jc.2005-0132. View

Guillermet-Guibert J, Lahlou H, Cordelier P, Bousquet C, Pyronnet S, Susini C . Physiology of somatostatin receptors. J Endocrinol Invest. 2006; 28(11 Suppl International):5-9. View

Dalm V, van Hagen P, Van Koetsveld P, Achilefu S, Houtsmuller A, Pols D . Expression of somatostatin, cortistatin, and somatostatin receptors in human monocytes, macrophages, and dendritic cells. Am J Physiol Endocrinol Metab. 2003; 285(2):E344-53. DOI: 10.1152/ajpendo.00048.2003. View

Patel Y . Somatostatin and its receptor family. Front Neuroendocrinol. 1999; 20(3):157-98. DOI: 10.1006/frne.1999.0183. View

10.

Yamada Y, Reisine T, Law S, Ihara Y, Kubota A, Kagimoto S . Somatostatin receptors, an expanding gene family: cloning and functional characterization of human SSTR3, a protein coupled to adenylyl cyclase. Mol Endocrinol. 1992; 6(12):2136-42. DOI: 10.1210/mend.6.12.1337145. View

11.

Yamada Y, Post S, Wang K, Tager H, Bell G, Seino S . Cloning and functional characterization of a family of human and mouse somatostatin receptors expressed in brain, gastrointestinal tract, and kidney. Proc Natl Acad Sci U S A. 1992; 89(1):251-5. PMC: 48214. DOI: 10.1073/pnas.89.1.251. View

12.

Corleto V, Nasoni S, Panzuto F, Cassetta S, Fave G . Somatostatin receptor subtypes: basic pharmacology and tissue distribution. Dig Liver Dis. 2004; 36 Suppl 1:S8-16. DOI: 10.1016/j.dld.2003.11.008. View

13.

Cakir M, Dworakowska D, Grossman A . Somatostatin receptor biology in neuroendocrine and pituitary tumours: part 1--molecular pathways. J Cell Mol Med. 2010; 14(11):2570-84. PMC: 4373477. DOI: 10.1111/j.1582-4934.2010.01125.x. View

14.

Zamora V, Cabanne A, Salanova R, Bestani C, Domenichini E, Marmissolle F . Immunohistochemical expression of somatostatin receptors in digestive endocrine tumours. Dig Liver Dis. 2009; 42(3):220-5. DOI: 10.1016/j.dld.2009.07.018. View

15.

Martin-Gago P, Rol A, Todorovski T, Aragon E, Martin-Malpartida P, Verdaguer X . Peptide aromatic interactions modulated by fluorinated residues: Synthesis, structure and biological activity of Somatostatin analogs containing 3-(3',5'difluorophenyl)-alanine. Sci Rep. 2016; 6:27285. PMC: 4895178. DOI: 10.1038/srep27285. View

16.

Kalkner K, Janson E, Nilsson S, Carlsson S, Oberg K, Westlin J . Somatostatin receptor scintigraphy in patients with carcinoid tumors: comparison between radioligand uptake and tumor markers. Cancer Res. 1995; 55(23 Suppl):5801s-5804s. View

17.

Johnbeck C, Knigge U, Kjaer A . PET tracers for somatostatin receptor imaging of neuroendocrine tumors: current status and review of the literature. Future Oncol. 2014; 10(14):2259-77. DOI: 10.2217/fon.14.139. View

18.

Waldherr C, Pless M, Maecke H, Schumacher T, Crazzolara A, Nitzsche E . Tumor response and clinical benefit in neuroendocrine tumors after 7.4 GBq (90)Y-DOTATOC. J Nucl Med. 2002; 43(5):610-6. View

19.

Bartsch D, Scherubl H . Neuroendocrine Tumors of the Gastrointestinal Tract. Visc Med. 2017; 33(5):321-322. PMC: 5697501. DOI: 10.1159/000481766. View

20.

Kaemmerer D, Peter L, Lupp A, Schulz S, Sanger J, Prasad V . Molecular imaging with ⁶⁸Ga-SSTR PET/CT and correlation to immunohistochemistry of somatostatin receptors in neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2011; 38(9):1659-68. DOI: 10.1007/s00259-011-1846-5. View