The incidence of neuroendocrine neoplasms (NENs) has been gradually increasing and most of NENs are located in gastroenteropancreatic system. With the application of target therapeutic drugs in recent years, the precise pathological diagnosis is required critically for effective clinical treatment: target therapy needs targeted pathological diagnosis. In this article, the definition of NENs, and the century-long evolution of diagnostic terms and grades are reviewed. The eight steps of pathological diagnosis of NENs for clinical needs are described. Four inconsistent concepts in NENs diagnosis are also discussed, that is immunohistochemical biomarkers of pathological diagnosis, subpopulation of neuroendocrine neoplasms with high proliferative activity, general adenocarcinomas with neuroendocrine differentiation and molecular genetics characteristics. To correctly understand these issues would be of great value for diagnosis and treatment of NENs.
Biomarkers, Tumor ; analysis ; Humans ; Immunohistochemistry ; Neoplasm Grading ; Neuroendocrine Tumors ; diagnosis ; pathology ; therapy ; Treatment Outcome

Antineoplastic Agents ; therapeutic use ; Colorectal Neoplasms ; classification ; drug therapy ; genetics ; pathology ; Humans ; Microsatellite Instability ; Mutation ; Polymorphism, Single Nucleotide ; Precision Medicine ; Proto-Oncogene Proteins ; genetics ; Proto-Oncogene Proteins B-raf ; genetics ; Proto-Oncogene Proteins p21(ras) ; ras Proteins ; genetics

Guanylin family, described in recent 10 years, is a series of small peptides (including guanylin, uroguanylin and lymphoguanylin) with structural and functional similarities to heat-stable enterotoxins (STs) elaborated by various pathogenic bacteria. They are abundance of cysteines and are endogenous activators of guanylyl cyclase-C (GC-C) receptors. Immunoreactive guanylin family peptides are localized in many human organs and tissues, especially in gastrointestinal tract and kidney, and play an important role in regulation of water and salt homeostasis. Recent studies showed that the mRNA levels of guanylin family peptides were down-regulated in colorectal cancers; oral intake of uroguanylin might suppress polyp formation in Apc(Min/+) mouse, and ~(111)In-labeled-ST peptide analog might specifically target human colon cancers. These evidences highlight that guanylin family may have a potential application in diagnosis and therapy effects of colorectal cancers.

Humans ; Molecular Epidemiology ; Pathology, Molecular ; Precision Medicine

Colorectal cancer (CRC), one of the most common malignant tumors, is caused both by environmental and genetic factors. Genetic factor plays an important role in the pathogenesis of CRC. Genome-wide association study (GWAS) is a new tool of genetic research. A series of susceptibility genes and loci of the complex diseases has been identified with GWAS strategy. In this article, the research progress on GWAS of CRC is reviewed, and the advantages and limitations of GWAS study as well as the prospective of its application are discussed.
Colorectal Neoplasms ; genetics ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Polymorphism, Single Nucleotide

OBJECTIVETo discover and identify differentially expressed genes associated with colorectal adenoma formation and the role of RegIV in colorectal adenoma differentiation.

METHODSA subtracted cDNA library was constructed with cDNAs that were isolated from either the normal mucosa or adenoma tissue of a single patient. Suppressive subtractive hybridization (SSH) combined with virtual northern blotting was used to characterize differentially expressed genes and contigs were assembled by electronic cloning (in silico cloning) with the EST database. Semi-quantitative RT-PCR was performed in 9 colorectal adenomas.

RESULTSThe amino acid sequence was determined with open reading frame (ORF) prediction software and was found to be 100% homologous to the protein product of RegIV (a novel gene isolated from a large inflammatory bowel disease library). RegIV was found to be highly expressed in all of the adenoma samples (9/9) compared with the normal mucosa samples, while 5/6 cases showed RegIV to be more strongly expressed in adenocarcinoma.

CONCLUSIONRegIV may play an important role in the initiation of colorectal adenoma differentiation, and its detection may be useful in the early diagnosis of colorectal adenoma formation.

Adenoma ; genetics ; metabolism ; Blotting, Northern ; Colorectal Neoplasms ; genetics ; metabolism ; Humans ; Lectins, C-Type ; biosynthesis ; genetics ; Nucleic Acid Hybridization ; Pancreatitis-Associated Proteins ; Prognosis ; Reverse Transcriptase Polymerase Chain Reaction

Renal cell carcinoma is a common type malignant tumor of the urinary system. The global incidence of renal cancer is 2. 2%. S100 proteins are involved in the regulations of proliferation, differentiation, apoptosis, and Ca2+ homeostasis, etc. S100 proteins are often closely associated with tumor progression. This review lists the expression changes of S100s and their functional significances in renal cancers, providing a new direction for the researches and treatments of renal cancer. The interpretation of S100 in the regulation of VHL/HIF signaling pathways should be a future direction.

Secretagogin (SCGN) is a novel member of EF-hand Ca2+-binding proteins, which was identified in islet β cells by Wagner. SCGN is a six EF-hand Ca2+-binding protein, primarily expressed on the neuroendocrine axis and the central nervous system. The protein has abundant biological functions. A certain concentration of calcium ion can lead to conformation change of SCGN, resulting in the change of intracellular signal transduction. Preliminary studies showed that SCGN would be used to treat stress reaction, such as mental illness (depression), burns or post-traumatic stress disorder and chronic stress reaction caused by pain. In Alzheimer's disease, the expression of SCGN in the hippocampus can boycott neurodegeneration. In neuroendocrine tumors, SCGN presents a good consistency with neuroendocrine markers such as CgA, Syn, and NSE, with a higher overall sensitivity and specificity. In addition, SCGN is released into serum after neural damage in cerebral ischemic diseases, suggesting that SCGN can be used as a marker for brain trauma. In this article, we review the recent research progress of secretagogin, focus on its distribution and functions in various tumorous diseases and non-tumorous diseases, such as Alzheimer's disease.
Alzheimer Disease ; diagnosis ; Biomarkers ; analysis ; Brain Ischemia ; diagnosis ; Calcium ; metabolism ; Hippocampus ; metabolism ; Humans ; Neuroendocrine Tumors ; diagnosis ; Secretagogins ; physiology ; Signal Transduction

Pulmonary neuroendocrine tumors are common in pathological practice and its pathological classification and histological grading are not exactly the same as that of those in the digestive tract and pancreas. In 2015 edition of World Health Organization classification, pulmonary neuroendocrine tumors are classified as carcinoid tumors (including typical carcinoid and atypical carcinoid), small cell lung carcinoma, large cell neuroendocrine carcinoma, and precursor lesion diffuse idiopathic neuroendocrine cell hyperplasia; each category has distinctive morphological and immunohistochemical features. The morphologic features including growth patterns and cytological appearances are keys for the diagnosis of neuroendocrine tumor, and immunohistochemical findings are also critical for its diagnosis. Furthermore, the diagnostic criteria vary for different types of specimen. In this article, we present a concise review and summary of the update of clinicopathological characterizations of pulmonary neuroendocrine tumor, with an emphasis on its diagnostic criteria and differential diagnosis.
Carcinoid Tumor ; diagnosis ; pathology ; Diagnosis, Differential ; Humans ; Hyperplasia ; Lung Neoplasms ; diagnosis ; pathology ; Neuroendocrine Tumors ; classification ; diagnosis ; pathology