Neuroendocrine Tumors of the Gastrointestinal Tract

Bartsch, Detlef K.; Scherübl, Hans

doi:10.1159/000481766

Cited by 6 publications

(5 citation statements)

References 7 publications

(3 reference statements)

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“…At present, few studies have assessed the IHC expression of SSTR in NENs, although IHC allows the correct identification of molecular targets in tumor cells and evaluation of different targeted therapeutic approaches. Patients with SSTR-positive tumors that are both advanced and aggressive are optimal candidates for peptide receptor radionuclide therapy (PRRT), increasing the overall survival rate and quality of life ( 28 ).…”

Section: Discussionmentioning

confidence: 99%

The new WHO classification of gastrointestinal neuroendocrine tumors and immunohistochemical expression of somatostatin receptor 2 and 5

et al. 2021

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The 2019 World Health Organization (WHO) classification of gastrointestinal tumors defines well-differentiated grade 3 neuroendocrine tumors, the mixed neuroendocrine-non-neuroendocrine tumors (MiNENs) and classifies goblet cell carcinoid as goblet cell adenocarcinoma. The expression of somatostatin receptors (SSTRs) is the foundation for somatostatin analogue therapy. At present, there are only a few studies that have analyzed the immunohistochemical reactivity of SSTRs in gastrointestinal neuroendocrine neoplasms (NENs). The aim of the present study was to evaluate the immunohistochemical expression of SSTR2 and SSTR5 in gastrointestinal NENs and goblet cell adenocarcinomas and the correlation of these markers with clinical and morphological factors. The study included 67 patients with NENs and 4 patients with adenocarcinoma ex-goblet cell carcinoid diagnosed between January 2008 and December 2018. Tumors were reclassified according to the 2019 WHO classification. Immunohistochemical staining for chromogranin A, synaptophysin, Ki-67, p53, SSTR2, and SSTR5 were performed in all the cases. The results showed that, G1 and G2 neuroendocrine tumors were more common SSTR2-positive in comparison with G3 carcinomas (P<0.0001). In addition, 33.3% of neuroendocrine carcinomas and 2 cases of low-grade adenocarcinoma ex-goblet cell carcinoid were SSTR2-positive. Neuroendocrine carcinomas had significantly lower SSTR2 and SSTR5 expression compared with well-differentiated neuroendocrine tumors (P=0.0130; P=0.0437, respectively). The SSTR2 expression in the early tumor stages was 100%, more often than in advanced stages (55.6%; P= 0.0011). The results demonstrated the decrease in SSTR2 expression with increasing malignancy and tumor stage. The SSTR2-positive expression in neuroendocrine carcinomas and adenocarcinoma ex-goblet cell carcinoid provides evidence for the benefits of somatostatin analog treatment associated with surgery and chemotherapy.

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Section: Discussionmentioning

confidence: 99%

The new WHO classification of gastrointestinal neuroendocrine tumors and immunohistochemical expression of somatostatin receptor 2 and 5

et al. 2021

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“…In addition, the increased incidence may be due to the increased prevalence and use of gastrointestinal endoscopy, resulting in a higher detection rate of GI-NETs ( 10 ). With the development of medical technology, in addition to conventional imaging examinations such as CT and MRI, more and more imaging techniques such as SSTR positron emission tomography/computed tomography (PET/CT) using 68Ga-labeled somatostatin analog ( 11 – 13 ) and endoscopic ultrasonography ( 14 , 15 ), have been used to detect tumors. These tests have greatly increased the detection of GI-NETs.…”

Section: Discussionmentioning

confidence: 99%

Trends in incidence and survival in patients with gastrointestinal neuroendocrine tumors: A SEER database analysis, 1977-2016

et al. 2023

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ObjectivesWe aimed to determine trends in incidence and survival in patients with gastrointestinal neuroendocrine tumors (GI-NETs) from 1977 to 2016, and then analyze the potential risk factors including sex, age, race, grade, Socioeconomic status (SES), site, and stage.MethodsData were obtained from Surveillance, Epidemiology, and End Results Program (SEER) database. Kaplan-Meier survival analysis, relative survival rates (RSRs), and Cox proportional risk regression model were used to evaluate the relationship between these factors and prognosis.ResultsCompared with other sites, the small intestine and rectum have the highest incidence, and the appendix and rectum had the highest survival rate. The incidence was higher in males than in females, and the survival rate in males was close to females. Blacks had a higher incidence rate than whites, but similar survival rates. Incidence and survival rates were lower for G3&4 than for G1 and G2. Age, stage, and grade are risk factors.ConclusionsThis study described changes in the incidence and survival rates of GI-NETs from 1977 to 2016 and performed risk factor analyses related to GI-NETs.

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“…1,2 Nevertheless, this entity represents the most frequent tumors within the small bowel with an annual incidence of 0.32-1.12/ 100,000 worldwide in recent years. [1][2][3][4] Furthermore, SI-NETs have a high tendency to metastasize-about 80% of patients have lymph node metastases (LNM) in the mesentery at the time of diagnosis. 5,6 In addition, around 50% of SI-NET patients develop mesenteric fibrosis (MF), a unique form of desmoplastic reaction in the mesentery, mostly associated with extensive fibrotic reaction around local LNM.…”

Section: Introductionmentioning

confidence: 99%

“…Neuroendocrine tumors of the small intestine (SI‐NETs) are rare and slowly growing neoplasms mostly arising from enterochromaffin cells 1,2 . Nevertheless, this entity represents the most frequent tumors within the small bowel with an annual incidence of 0.32–1.12/100,000 worldwide in recent years 1‐4 . Furthermore, SI‐NETs have a high tendency to metastasize—about 80% of patients have lymph node metastases (LNM) in the mesentery at the time of diagnosis 5,6 .…”

Section: Introductionmentioning

confidence: 99%

Mesenteric fibrosis in patients with small intestinal neuroendocrine tumors is associated with enrichment of alpha‐smooth muscle actin‐positive fibrosis and COMP‐expressing stromal cells

Graf,

Keber,

Hattesohl

et al. 2024

J Neuroendocrinology

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Neuroendocrine tumors of the small intestine (SI‐NETs) often develop lymph node metastasis (LNM)‐induced mesenteric fibrosis (MF). MF can cause intestinal obstruction as well as ischemia and render surgical resection technically challenging. The underlying pathomechanisms of MF are still not well understood. We examined mesenteric LNM and the surrounding stroma compartment from 24 SI‐NET patients, including 11 with in situ presentation of strong MF (MF+) and 13 without MF (MF−). Differential gene expression was assessed with the HTG EdgeSeq Oncology Biomarker Panel comparing MF+ with MF− within LNM and paired stromal samples, respectively. Most interesting differentially expressed genes were validated by reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR) in combination with validation of associated protein levels utilizing immunohistochemistry (IHC) staining of MF+ and MF– formalin‐fixed, paraffin‐embedded (FFPE) patient samples. Overall, 14 genes measured with a 2549‐gene expression panel were differentially expressed in MF+ patients compared to MF−. Of those, nine were differentially expressed genes in LNM and five genes in the stromal tissue (>2‐fold change, p < .05). The top hits included increased COMP and COL11A1 expression in the stroma of MF+ patients compared to MF−, as well as decreased HMGA2, COL6A6, and SLC22A3 expression in LNM of MF+ patients compared to LNM of MF− patients. RT‐qPCR confirmed high levels of COMP and COL11A1 in stroma samples of MF+ compared to MF− patients. IHC staining confirmed the enrichment of α‐smooth muscle actin‐positive fibrosis in MF+ compared to MF− patients with corresponding increase of COMP‐expressing stromal cells in MF+. Since COMP is associated with the known driver for fibrosis development transforming growth factor beta and with a cancer‐associated fibroblasts enriched environment, it seems to be a promising new target for MF research.

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Neuroendocrine Tumors of the Gastrointestinal Tract

Cited by 6 publications

References 7 publications

The new WHO classification of gastrointestinal neuroendocrine tumors and immunohistochemical expression of somatostatin receptor 2 and 5

The new WHO classification of gastrointestinal neuroendocrine tumors and immunohistochemical expression of somatostatin receptor 2 and 5

Trends in incidence and survival in patients with gastrointestinal neuroendocrine tumors: A SEER database analysis, 1977-2016

Mesenteric fibrosis in patients with small intestinal neuroendocrine tumors is associated with enrichment of alpha‐smooth muscle actin‐positive fibrosis and COMP‐expressing stromal cells

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