gastrin-releasing-peptide and Neuroendocrine-Tumors

Neuroendocrine differentiation of prostate cancer (PCa) is a relatively frequent event, generally understudied, that carries important prognostic information. It is the most frequently observed during the advanced stages of disease, when PCa has lost its sensitivity to androgen deprivation therapy or to chemotherapy, moderate to diffuse bone metastatic spread dominates the imaging scenario and it is responsible for painful clinical symptomatology. However, evidences indicate that neuroendocrine differentiation is a progressive phenomenon that starts at the very early part of the pathogenesis of cancer transformation contributing to it. Neuroendocrine tumor phenotypes have reduced capability to secrete the prostate specific antigen (PSA) and therefore PSA does not represent a reliable marker to follow-up neuroendocrine differentiation. Tumor progression may be monitored by measuring plasma concentration of neuroendocrine tumor markers, primarily chromogranin A and neuron-specific enolase. Several nuclear medicine tracers are available for studying different biochemical properties of tumor cells with neuroendocrine differentiation. Single photon computed emission tomography (SPECT) with [111In-diethylenetriaminepentaacetic acid] ([111In-DTPA0])- octreotide (Octreoscan) has been extensively used in the past. However, the development of the chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), which in comparison to DTPA allows higher affinity bindings for beta-emitting radionuclides and for somatostatin (SST) analogues, and the increased availability of the Germanium-68/Gallium-68 (68Ge/68Ga)-generator, which enables positron emission tomography/computed tomography (PET/CT) imaging, have allowed the synthesis of several PET tracers for different SST receptors. The receptor of the bombesin/ gastrin releasing peptide (GRP), which is overexpressed in PCa with neuroendocrine differentiation, also represents an innovative research field with diagnostic and therapeutic applications through, respectively, positron and beta emitters. At the moment, however, we observe some discrepancy between the high number of preclinical studies and the small number of clinical studies, most likely related to competing and, at the moment, more effective radiopharmaceuticals for imaging and for radiometabolic therapy, such PET/CT with radiolabeled choline and prostate-specific membrane antigene (PSMA)-ligands, the latter being labeled either with 68Ga for imagin

Topics: Bombesin; Gallium Radioisotopes; Gastrin-Releasing Peptide; Germanium; Heterocyclic Compounds, 1-Ring; Humans; Male; Neuroendocrine Tumors; Pentetic Acid; Phenotype; Positron Emission Tomography Computed Tomography; Prostatic Neoplasms; Radioisotopes; Radiopharmaceuticals; Somatostatin; Tomography, Emission-Computed, Single-Photon

Progastrin-releasing peptide (proGRP) is a recently identified biomarker of small-cell lung cancer. In well-differentiated neuroendocrine tumours (WDNETs), this study investigates the association between proGRP and tumour characteristics and the prognostic value of proGRP levels compared with chromogranin A (CgA) levels.. Serum samples were obtained in 282 patients with WDNET. The receiver operating characteristic (ROC) curve technique was used to assess specificity and sensitivity in the identification of a primary tumour location. Cox proportional hazards models and Kaplan-Meier curves were constructed to determine the association of patients' characteristics and tumour markers with survival.. For proGRP, the ROC curve indicated a cut-off level of 90 ng/l (approximately twice the upper reference value), with a specificity of 99% and a sensitivity of 43% in distinguishing primary pulmonary tumours from other sites. In the multivariate Cox model, both proGRP and CgA were strongly associated with survival (P < 0.0001 for both variables).. A high-risk proGRP level (more than twice the upper reference value) in patients with WDNETs is a strong indication for a primary tumour in the lung. Besides CgA, proGRP is a complementary tumour marker for prognosis and treatment monitoring in patients with neuroendocrine tumour.

Topics: Adult; Aged; Biomarkers, Tumor; Case-Control Studies; Female; Gastrin-Releasing Peptide; Gastrointestinal Neoplasms; Humans; Kaplan-Meier Estimate; Lung Neoplasms; Male; Middle Aged; Multivariate Analysis; Neuroendocrine Tumors; Proportional Hazards Models; ROC Curve

Non-small cell lung cancers with neuroendocrine differentiation (NSCLC-NE) may demonstrate biologic behavior intermediate between non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) with impact on prognosis. We studied the expression of four well-defined neuroendocrine (NE) markers: neuron-specific enolase (NSE), chromogranin A, Leu-7, gastrin-releasing peptide, and a panel of three non-NE markers, including vimentin, and the epithelial markers carcino-embryonic antigen (CEA) by immunohistochemistry, and mucin by histochemistry in 237 resected NSCLCs from patients on six LCSG protocols. Twenty-nine (12%) tumors were positive for 2 or more NE markers. An NE differentiation score was calculated but failed to correlate with recurrence as did other combinations of markers. However, the presence of tissue staining for CEA was strongly associated with improved survival (p = 0.011), whereas the presence of mucin was associated with a worse outcome (p < 0.001). Individually, CEA and mucin remained prognostic even when corrected for stage, histologic features, and performance status. We conclude that NE differentiation is not predictive of recurrence in patients with resected NSCLC but data on patterns of CEA and mucin expression may improve prognostication and permit rational design of new therapeutic approaches.

Topics: Antigens, Differentiation; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Non-Small-Cell Lung; Chromogranin A; Chromogranins; Gastrin-Releasing Peptide; Humans; Immunohistochemistry; Lung Neoplasms; Neoplasm Recurrence, Local; Neuroendocrine Tumors; Peptides; Phosphopyruvate Hydratase; Prognosis; Proportional Hazards Models; Vimentin