Is Ectopic Cushing Syndrome Commonly Associated with Small Cell Lung Cancer (SCLC)? Critical Review of the Literature and ACTH Expression in Resected SCLC.

The literature emphasizes that pulmonary ectopic Cushing syndrome (ECS) is associated not only with neuroendocrine tumors (NETs), but also with small cell lung carcinomas (SCLCs). This statement is debatable, because extrapulmonary ECS is associated with NETs in the vast majority of cases and very rarely with neuroendocrine carcinomas (NECs). Therefore, we critically reviewed the literature on SCLCs associated with ECS (ECS-SCLC) and performed immunohistochemical analysis of ACTH expression in 155 resected SCLCs and 158 pulmonary NETs.

Trends in the Management and Outcomes of Neuroendocrine Liver Metastases: A Three-decade, Multi-centre Observational Cohort Study.

Objective: To describe the evolution of management strategies for neuroendocrine liver metastases (NE LM) and trends in patient outcomes over the preceding 3 decades.

Summary Background Data: Liver metastases are common in neuroendocrine neoplasms and impair prognosis. A broad therapeutic armamentarium has evolved over recent decades but there remains uncertainty regarding optimal treatment selection and sequencing.

[Anaphylactic shock after mistletoe therapy].

Life-threatening side effects of mistletoe therapy are mostly negated by physicians working in complementary medicine. This article reports on a case of life-threatening anaphylactic shock after carrying out mistletoe therapy. In patients with a carcinoid syndrome (flushes, diarrhea, bronchoconstriction) the diagnosis of anaphylactic shock can be masked by the findings of a neuroendocrine neoplasm.

Expression of FAM159B in Humans, Rats, and Mice: A Cross-species Examination.

Little is known about the adaptor protein FAM159B. To determine whether FAM159B expression findings in rats or mice can be extrapolated to humans, we compared FAM159B expression in healthy tissue samples from all three species using immunohistochemistry. Despite variations in expression intensity, similar FAM159B expression patterns were observed in most organs across species.

Expression of free fatty acid receptor 2 in normal and neoplastic tissues.

Objective: Little information is available concerning protein expression of the free fatty acid receptor 2 (FFAR2), especially in tumours. Therefore, the aim of the present study was to comprehensively characterise the expression profile of FFAR2 in a large series of human normal and neoplastic tissues using immunohistochemistry thus providing a basis for further in-depth investigations into its potential diagnostic or therapeutic importance.

Methods: We developed a novel rabbit polyclonal anti-FFAR2 antibody, 0524, directed against the C-terminal region of human FFAR2.

Expression of G protein-coupled receptor GPR19 in normal and neoplastic human tissues.

Little is known about the expression of the orphan G protein-coupled receptor GPR19 at the protein level. Therefore, we developed a rabbit antibody, targeting human GPR19. After verification of the antibody specificity using GPR19-expressing cell lines and a GPR19-specific siRNA, the antibody was used for immunohistochemical staining of a variety of formalin-fixed, paraffin-embedded normal and neoplastic human tissue samples.

Expression of the Calcitonin Receptor-like Receptor (CALCRL) in Normal and Neoplastic Tissues.

Little information is available concerning protein expression of the calcitonin receptor-like receptor (CALCRL) at the protein level. Here, we developed a rabbit monoclonal antibody, 8H9L8, which is directed against human CALCRL but cross-reacts with the rat and mouse forms of the receptor. We confirmed antibody specificity via Western blot analyses and immunocytochemistry using the CALCRL-expressing neuroendocrine tumour cell line BON-1 and a CALCRL-specific small interfering RNA (siRNA).

Hemicolectomy versus appendectomy for patients with appendiceal neuroendocrine tumours 1-2 cm in size: a retrospective, Europe-wide, pooled cohort study.

Background: Awareness of the potential global overtreatment of patients with appendiceal neuroendocrine tumours (NETs) of 1-2 cm in size by performing oncological resections is increasing, but the rarity of this tumour has impeded clear recommendations to date. We aimed to assess the malignant potential of appendiceal NETs of 1-2 cm in size in patients with or without right-sided hemicolectomy.

Methods: In this retrospective cohort study, we pooled data from 40 hospitals in 15 European countries for patients of any age and Eastern Cooperative Oncology Group performance status with a histopathologically confirmed appendiceal NET of 1-2 cm in size who had a complete resection of the primary tumour between Jan 1, 2000, and Dec 31, 2010.

Co-Expression of Adaptor Protein FAM159B with Different Markers for Neuroendocrine Cells: An Immunocytochemical and Immunohistochemical Study.

Little is known about the adaptor protein FAM159B. Recently, FAM159B was shown to be particularly expressed in neuroendocrine cells and tissues, such as pancreatic islets and neuroendocrine cells of the bronchopulmonary and gastrointestinal tracts, as well as in different types of neuroendocrine tumours. To gain insights into possible interactions of FAM159B with other proteins and/or receptors, we analysed the co-expression of FAM159B and various neuroendocrine-specific markers in the cancer cell lines BON-1, PC-3, NCI-h82, OH-1, and A431 and also in human pancreatic tissues and pancreatic neuroendocrine tumours.

Evaluation of PD-L1 expression in a large set of gastroenteropancreatic neuroendocrine tumours and correlation with clinicopathological data.

Background: Targeting programmed death protein 1 (PD-1) or its ligand PD-L1 is a promising therapeutic approach for many types of cancer in which PD-L1 is overexpressed. However, data on PD-L1 expression levels in gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are limited and contradictory.

Methods: We evaluated PD-L1 expression in 457 archived, formalin-fixed, paraffin-embedded GEP-NEN samples from 175 patients by immunohistochemistry using the highly sensitive monoclonal anti-PD-L1 antibody 73-10.

Reassessment of somatostatin receptor SST4 expression in bronchopulmonary and gastroenteropancreatic neuroendocrine neoplasms using the novel rabbit monoclonal anti-human SST4 antibody 7H49L61.

Somatostatin receptors SST1, SST2, and SST5 are overexpressed in neuroendocrine neoplasms (NENs), but little is known about SST4 expression in NENs because of a lack of specific monoclonal antibodies. We recently developed and thoroughly characterised a rabbit monoclonal anti-human SST4 antibody, 7H49L61, and showed that it is well suited for identifying SST4 expression in routine pathology samples. The present study aimed to re-evaluate SST4 expression in a large set of NEN samples using this antibody.

Comparative evaluation of somatostatin and CXCR4 receptor expression in different types of thyroid carcinoma using well-characterised monoclonal antibodies.

Background: Papillary and follicular thyroid carcinomas can be treated surgically and with radioiodine therapy, whereas therapeutic options for advanced stage IV medullary and for anaplastic tumours are limited. Recently, somatostatin receptors (SSTs) and the chemokine receptor CXCR4 have been evaluated for the treatment of thyroid carcinomas, however, with contradictory results.

Methods: The expression of the five SSTs and of CXCR4 was assessed in 90 samples from 56 patients with follicular, papillary, medullary, or anaplastic thyroid carcinoma by means of immunohistochemistry using well-characterised monoclonal antibodies.

Assessment of G Protein-Coupled Oestrogen Receptor Expression in Normal and Neoplastic Human Tissues Using a Novel Rabbit Monoclonal Antibody.

In addition to the classical oestrogen receptors, ERα and ERβ, a G protein-coupled oestrogen receptor (GPER) has been identified that primarily mediates the rapid, non-genomic signalling of oestrogens. Data on GPER expression at the protein level are contradictory; therefore, the present study was conducted to re-evaluate GPER expression by immunohistochemistry to obtain broad GPER expression profiles in human non-neoplastic and neoplastic tissues, especially those not investigated in this respect so far. We developed and thoroughly characterised a novel rabbit monoclonal anti-human GPER antibody, 20H15L21, using Western blot analyses and immunocytochemistry.

Immunohistochemical Evaluation of Adaptor Protein FAM159B Expression in Normal and Neoplastic Human Tissues.

FAM159B is a so-called adaptor protein. These proteins are essential components in numerous cell signalling pathways. However, little is known regarding FAM159B expression in normal and neoplastic human tissues.

Clinical Features and Prognosis of Patients with Carcinoid Syndrome and Carcinoid Heart Disease: A Retrospective Multicentric Study of 276 Patients.

Introduction: Carcinoid syndrome is the most frequent functional syndrome of neuroendocrine neoplasia. It is characterized by flushing, diarrhea, wheezing, hypotension, and exanthema and may cause carcinoid heart disease.

Methods: We assessed clinical characteristics and prognosis of patients with carcinoid syndrome and carcinoid heart disease in 276 patients from 3 referral centers.

A combination of surgery, theranostics, and liquid biopsy - a personalised oncologic approach to treatment of patients with advanced metastatic neuroendocrine neoplasms.

Neuroendocrine neoplasia (NEN) of small bowel (SBNEN) frequently present with metastatic disease. Theranostics (molecular imaging followed by targeting therapy) allow for personalised medicine. Liquid biopsies enable precise identification of residual disease and real-time monitoring of therapeutic response.

Primary Neuroendocrine Neoplasia of the Liver.

The presence of primary neuroendocrine tumors in the liver is still a matter of controversy. We present a case of a somatostatin-receptor-positive mass of the liver in the 68Ga-DOTATOC PET/CT. No other primary tumor was found after conventional imaging, endoscopically, and after liver-segment resection.

Immunohistochemical identification of complement peptide C5a receptor 1 (C5aR1) in non-neoplastic and neoplastic human tissues.

The complement component C5a and its receptor C5aR1 are involved in the development of numerous inflammatory diseases. In addition to immune cells, C5aR1 is expressed in neoplastic cells of multiple tumour entities, where C5aR1 is associated with a higher proliferation rate, advanced tumour stage, and poor patient outcomes. The aim of the present study was to obtain a broad expression profile of C5aR1 in human non-neoplastic and neoplastic tissues, especially in tumour entities not investigated in this respect so far.

Prognostic value of PD-L1 expression in bronchopulmonary neuroendocrine tumours.

Programmed death protein 1 (PD-1) and its ligand, PD-L1, have emerged as promising therapeutic targets for many types of cancer that overexpress PD-L1. However, data on PD-L1 expression levels in bronchopulmonary neuroendocrine neoplasms (BP-NEN) are limited and contradictory. In the present study, a total of 298 archived, formalin-fixed, paraffin-embedded BP-NEN samples from 97 patients diagnosed with typical carcinoid (TC), atypical carcinoid (AC), small cell lung cancer (SCLC), or large cell neuroendocrine carcinoma of the lung (LCNEC) were evaluated for PD-L1 expression by immunohistochemistry using the highly sensitive monoclonal anti-PD-L1 antibody 73-10.

Immunoprofiling in Neuroendocrine Neoplasms Unveil Immunosuppressive Microenvironment.

Checkpoint inhibitors have shown promising results in a variety of tumors; however, in neuroendocrine tumors (NET) and neuroendocrine carcinomas (NEC), low response rates were reported. We aimed herein to investigate the tumor immune microenvironment in NET/NEC to determine whether checkpoint pathways like programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) might play a role in immune escape and whether other escape mechanisms might need to be targeted to enable a functional antitumor response. Forty-eight NET and thirty NEC samples were analyzed by immunohistochemistry (IHC) and mRNA immunoprofiling including digital spatial profiling.

Radical intended surgery for highly selected stage IV neuroendocrine neoplasms G3.

Background: Stage IV gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs) G3 are the NENs with the worst prognosis. According to ENETS guidelines, platinum-based chemotherapy is the standard treatment for this population. Surgery is only considered in highly selected "resectable" NENs with usually lower Ki67.

Surgery with Radical Intent: Is There an Indication for G3 Neuroendocrine Neoplasms?

Background: While platinum-based chemotherapy represents the standard treatment for advanced grade 3 (G3) neuroendocrine neoplasms (NENs) according to the European Neuroendocrine Tumor Society guidelines, the role of radical-intended surgery in these patients, as well as the use of adjuvant chemotherapy, are still controversial. The aim of the present work is to describe, in a retrospective series of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) G3, the overall survival (OS) rate and risk factors for death after radical surgery. Secondary aims are the description of median recurrence-free survival (RFS) and of the role of adjuvant chemotherapy.

Comprehensive Assessment of GPR68 Expression in Normal and Neoplastic Human Tissues Using a Novel Rabbit Monoclonal Antibody.

GPR68 (OGR1) belongs to the proton-sensing G protein-coupled receptors that are involved in cellular adaptations to pH changes during tumour development. Although expression of GPR68 has been described in many tumour cell lines, little is known about its presence in human tumour entities. We characterised the novel rabbit monoclonal anti-human GPR68 antibody 16H23L16 using various cell lines and tissue specimens.

Somatostatin and chemokine CXCR4 receptor expression in pancreatic adenocarcinoma relative to pancreatic neuroendocrine tumours.

Purpose: Pancreatic adenocarcinoma (PAC) represents one of the most fatal types of cancer with an exceptionally poor prognosis, underscoring the need for improved diagnostic and treatment approaches. An over-expression of somatostatin receptors (SST) as well as of the chemokine receptor CXCR4 has been shown for many tumour entities. Respective expression data for PAC, however, are scarce and contradictory.

Different somatostatin and CXCR4 chemokine receptor expression in gastroenteropancreatic neuroendocrine neoplasms depending on their origin.

Somatostatin receptors (SST), especially SST2A, are known for their overexpression in well-differentiated gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN). The chemokine receptor CXCR4, in contrast, is considered to be present mainly in highly proliferative and advanced tumors. However, comprehensive data are still lacking on potential differences in SST or CXCR4 expression pattern in GEP-NEN in dependence on the place of origin.