gastrin-releasing-peptide and Carcinoma--Neuroendocrine

Serum calcitonin (CT) is pivotal in medullary thyroid cancer (MTC) management. Recently, progastrin releasing peptide (ProGRP) has been proposed as a candidate complementary tumor marker of MTC. As current data are sparse our study was undertaken to evaluate the distribution of ProGRP in patients with MTC and its relationship with the tumor burden. Additionally, serial measurement of CT, carcinoembryonic antigen (CEA) and ProGRP was evaluated in three patients undergoing tyrosine kinase inhibitors (TKI).. Seventy-eight, 125 and 62 sera from patients with MTC, non-medullary malignant and benign thyroid diseases were collected, respectively. ProGRP measurement was performed by Elecsys. Significantly higher ProGRP levels were found in MTC compared to non-MTC patients. Among MTC patients ProGRP levels accurately discriminate patients with active from those with cured disease and, respectively, patients with loco-regional active disease from those with distant metastasis. Finally, ProGRP performed better than CT and CEA in monitoring the response to TKI therapy in three patients monitored serially.. Serum ProGRP is promising as a complementary tumor marker in MTC patients. Further studies will be required, mainly focused on monitoring ProGRP during TKI treatment for early detection of resistance and assessing its usefulness to avoid the observed false positive fluctuations that occur with CT and carcinoembryonic antigen.

Topics: Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Neuroendocrine; Gastrin-Releasing Peptide; Humans; Peptide Fragments; Recombinant Proteins; Thyroid Neoplasms

It is well known that small cell neuroendocrine carcinoma (SNEC) arising at extrapulmonary sites has a poor prognosis and an interesting biological characterization. To understand biological characterization and elucidation of the origin of the histogenesis of SNEC, we report the establishment of a new SNEC cell line and characteristics of neuroendocrine properties including neuronal differentiation by treatment with dibutyryl cyclic AMP (db-cAMP).. We established a new cell line (SNEC-MI) derived from SNEC of the maxillary sinus by a modified spill-out method, and verified neuroendocrine properties including neuronal differentiation by immunocytochemical and immunoblotting methods.. The established cell line showed spherical or spindle shape in monolayer culture and was positive for neuron-specific enolase (NSE), neuronal cell adhesion protein (N-CAM, CD56) and gastrin-releasing peptide. NSE was also demonstrated in the cultured medium and dense-core neuroendocrine granules were detected ultrastructurally in the cytoplasm. Treatment of cells with db-cAMP markedly induced the development and elongation of neuronal processes, which formed a netlike arrangement. Characterization of these elongated neuronal processes revealed them immunoreacting intensely with high molecular-weight neurofilament, and a time-dependent increase of microtubule-associated protein-2 in cell lysates.. These findings indicated that this cell line possesses the capability to differentiate into neuronal cells, and supported the hypothesis that extrapulmonary SNEC might be derived from a pluripotent stem cell.

Topics: Animals; Blotting, Western; Bucladesine; Carcinoma, Neuroendocrine; Carcinoma, Small Cell; Cell Adhesion Molecules; Cell Differentiation; Cell Line, Tumor; Chromosome Aberrations; DNA, Neoplasm; Gastrin-Releasing Peptide; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Lymphatic Metastasis; Maxillary Sinus Neoplasms; Mice; Mice, Inbred BALB C; Mice, Nude; Neurons; Phenotype; Phosphopyruvate Hydratase; Polymerase Chain Reaction

We report herein the first documented case of gastrin-releasing peptide-positive neuroendocrine (NE) carcinoma of the extrahepatic biliary tract. An invasive tumor measuring 2.5 x 1.5 cm was located in the confluence portion of the cystic duct in a 70-year-old Japanese man. Histologically, the tumor was found to be composed of small polygonal cells which formed a solid and trabecular structure, and the frequencies of both mitoses and small necrotic areas were dominant. The tumor cells were immunoreactive to the NE markers chromogranin-A and neuron-specific enolase, as well as to carcinoembryonic antigen and gastrin-releasing peptide. Although a few cases of gastrin-releasing peptide-positive small-cell lung carcinoma have been documented, there have been no reports of gastrin-releasing peptide-positive NE carcinoma occurring in the gastrointestinal tract. We consider our case not merely to be of pathological interest, but also to have clinical and therapeutic implications.

Topics: Aged; Bile Duct Neoplasms; Bile Ducts, Extrahepatic; Carcinoma, Neuroendocrine; Chromogranin A; Chromogranins; Fatal Outcome; Gastrin-Releasing Peptide; Humans; Immunohistochemistry; Male; Phosphopyruvate Hydratase