Introduction: The purpose of this study was to determine the possible differences in genetic polymorphisms and serum levels of chromogranin A (CgA), according to age and sex, in subjects with and without metabolic syndrome (MetS). Methodology: The genotyping and serum level of CgA and biochemical parameters were measured by the T-ARMS-PCR and PCR-RFLP and ELISA and spectrophotometer methods, respectively. Results: A comparison of males with and without MetS showed significantly lower high-density lipoprotein-cholesterol (HDL-C) levels than those of females. At ages 30-70 years, both sexes showed significant differences in triglycerides (TG), fasting blood sugar (FBS), CgA levels and waist circumference (WC) when compared to the two groups. Both sexes with MetS indicated significant differences in systolic blood pressure (SBP) at ages 40-70 years, while at ages 40-59 years, there was a significant difference in HDL-C level in males. There was a significant correlation between serum levels of FBS, TG, SBP and WC (in both sexes), and CgA in subjects with MetS. Significant correlation was found between HDL-C level and diastolic blood pressure (DBP), and CgA level in males and females, respectively. CgA genotype frequency (T-415C and C+87T polymorphisms) showed no significant differences between males and females with and without MetS, while there was only a significant difference in frequency of the genotypes T-415C when compared to males with and without MetS. Conclusion The CgA appears to be strongly associated with MetS components in both sexes. Variation in CgA gene expression may affect the T–415C polymorphism in males. This may mean that the structure of CgA genetics differs in different ethnic groups. Differences in the serum level and expression of CgA gene may show valuable study results that it may be expected a relationship between these variables and the MetS.
Sex ; Chromogranin A ; Genotype ; Metabolic Syndrome

OBJECTIVE: To investigate the clinical features, diagnosis, treatments and prognosis for gastrointestinal neuroendocrine tumors (GI-NETs).
 METHODS: Clincal data of 52 patients, who were diagnosed as GI-NETs between January 2004 and October 2014, were reviewed. The patients were divided into a local excision group (n=21) and a transabdominal excision group (n=30), and the major clinical features, treatment modalities and outcomes were analyzed.
 RESULTS: The clinical features of GI-NETs were nonspecific, and most of the clinical manifestation were local invasiveness. CT scan was lack of specific findings. GI-NETs greater than 1 cm often showed local incrassation, upheaval and soft tissue shadow. In the case of lager GI-NETs, necrosis and moderate enhancement could be seen. Positive ratio for expression of chromogranin A (CgA) and synaptophysin (Syn) in the 52 cases of specimen were 63.5% and 88.5%, respectively. Except 1 patient, whose surgery was canceled because of poor health, other 51 patients were treated with surgery through different approaches. Among them, 30 cases were transabdominal resection (57.7%) and 21 were local resection (40.4%). Chemotherapy and/or radiotherapy was only applied for 7 patients. After a follow-up of 40 (3-132) months, 7 patients died, the rest were alive. The median survival in the local resection group and the transabdominal resection group was 43.0 and 39.5 months, respectively (P>0.05).
 CONCLUSION Under the condition of fully understanding the biological characteristics of GI-NETs, early diagnosis and timely personalized treatment is hopeful to reach the relative good prognosis and survival.
Chromogranin A ; Gastrointestinal Neoplasms ; Humans ; Neuroendocrine Tumors ; Prognosis

The purpose of this study was to determine if salivary chromogranin a secretion in dogs exhibits a circadian rhythm. Saliva sampling was performed during three different sessions occurring in three nonconsecutive 24-h periods. Sixteen healthy adult beagle dogs (8 males and 8 females) were moved to a sampling room and housed individually in cages. Saliva samples were obtained every 4 h from 12:00 p.m. to 12:00 p.m. the following day. In the interest of habituation, saliva was obtained hourly from each dog 3 h before the experiment was started. Salivary chromogranin A concentrations were measured using an enzyme-linked immunosorbent assay. No circadian rhythm was detected for salivary chromogranin A secretion, and no differences in salivary chromogranin A concentrations measured every 4 h were demonstrated during the 24-h cycle in dogs.
Animals ; Chromogranin A/*analysis/*metabolism ; *Circadian Rhythm ; Dogs/*physiology ; Saliva/*chemistry

Predominant type of serum prostate specific antigen (PSA) is a complexed-form which is bound to alpha-1-antichymotrypsin (ACT). Major fraction of serum ACF is derived from the liver and ACT has recently been demonstrated to be produced by PSA-producing prostatic epithelium as well. However, the feature and significance of prostate-derived ACT remain ill-defined. We herein immunohistochemically studied prostatic tissues in 40 patients with prostate cancer and 20 patients with benign prostatic hyperplasia (BPH) using antibody to ACT, cytokeratin AE3 and chromogranin A. In normal portion of prostate, secretory epithelia of central zone and peripheral zone, and basa1 cells and neuroendocrine cells of peripheral zone showed positive staining for ACT. Benign hyperplastic prostatic gland did not stain for ACT. On the study of prostate cancer tissues, relatively increased staining for ACT were found in solid and infiltrative type of cancer cells and high grade cancer cells. High intensity staining for ACT were observed in normal prostatic tissues adjacent to invasive cancer cells. In conclusions, basal cells as well as secretory epithelia of the normal prostate gland may be the source of serum ACT production by prostate cancer may be closely related with its malignant and invasive potential.
Chromogranin A ; Epithelium ; Humans ; Immunohistochemistry ; Keratins ; Liver ; Neuroendocrine Cells ; Prostate* ; Prostate-Specific Antigen ; Prostatic Hyperplasia ; Prostatic Neoplasms*

PURPOSE: Neuroendocrine (NE) cells in a prostate carcinoma may play important roles in tumor growth, proliferation and progression. The aim of this study was to evaluate the relationship between the NE cell differentiation status and pathological characteristics of prostate cancer. MATERIALS AND METHODS: Radical prostatectomy specimens from 215 patients were available for analysis. NE cell were detected by immunohistochemistry, using antibodies to chromogranin A (CgA). Tumor cell proliferation was assessed using the Ki-67 proliferation index (PI) employing the MIB-1 antibody. Staining of CgA was scored as: 0= no staining; 1= staining cell < 10; 2= staining 10-20; and 3= staining cell >20. Tumors were classified depending on their staining score, positive staining and growth pattern. RESULTS: NE cell differentiation was present in 25.1% (54/215) of tumors. The amount of NE cells significantly increased; from tumors with solitary scattered NE cells to both small and large clusters (p<0.05). NE cell differentiation and the growth pattern were correlated with the Ki-67 PI (p<0.05). With respect to high-grade tumors, an increased PI was found in tumors with positive NE cells compared with those with negative NE (p<0.05). Pathologically advanced tumors, or those with higher histological grades, were associated with NE cell differentiation and Ki-67 PI (p<0.05). CONCLISIONS: NE cell differentiation in prostate cancer may lead to increased proliferation, high-grade tumors and an advanced stage. The exact prognostic significance of NE still has to be addressed in larger prospective, comparative and highly selective clinical studies.
Antibodies ; Cell Differentiation ; Cell Proliferation ; Chromogranin A ; Humans ; Immunohistochemistry ; Neuroendocrine Cells* ; Prostate* ; Prostatectomy ; Prostatic Neoplasms*

Pancreas is an endocrine organ as well as an exocrine one. The pancreatic neuroendocrine tumor (PNET) is an epithelial tumor with features of endocrine differentiation. Its incidence is progressively increasing now. Because the prognosis of PNET is much better than that of ductal adenocarcinoma, the precise diagnosis and proper treatment is more important than ever. Recently World Health Organization (WHO) and American Joint Committee on Cancer (AJCC) published the new WHO 2010 classification and the unified staging system of the PNET unlike the other gastrointestinal tract. Here, recent update of pathology of PNET will be discussed with their basic morphologic characteristics and essential points in the pathology report.
Adenocarcinoma ; Chromogranin A ; Gastrointestinal Tract ; Incidence ; Joints ; Neuroectodermal Tumors, Primitive ; Neuroendocrine Tumors ; Pancreas ; Prognosis ; World Health Organization

PURPOSE: This study was undertaken to evaluate the significance of cyclooxygenase-2 (COX2) overexpression and the expression of somatostatin receptor (SSTR) subtypes in gastroenteropancreatic neuroendocrine tumors (GEP-NETs). MATERIALS AND METHODS: Two hundred and forty-seven cases of GEP-NET, comprising 86 foregut and 156 hindgut primary NETs, and 5 metastatic NETs in the liver, were studied retrospectively with immunohistochemistry for COX2, chromogranin A, Ki-67, SSTR1, SSTR2, and SSTR5. RESULTS: COX2 overexpression was observed in 54%(126 of 234), and SSTR1, SSTR2, and SSTR5 positivity in 84%(196 of 233), 72%(168 of 233), and 55%(128 of 232), respectively. COX2 overexpression was found to be positively correlated with Ki-67 labeling index and inversely correlated with the expression of SSTR subtypes. In addition, the expression of SSTR subtypes was tightly correlated in any comparative pairs. A significant inverse correlation was found between COX2 and SSTR2 expression in the foregut, but not hindgut NETs. Kaplan-Meier analyses showed that COX2 overexpression (p=0.003) and high Ki-67 labeling index (p<0.001) were associated with poor overall survival (OS), whereas expression of SSTR2 (p<0.001) was associated with better OS of GEP-NET patients. Multivariate analysis revealed negative SSTR2 expression as an independent prognostic marker in GEP-NET patients (p<0.001). CONCLUSION: Our results suggest that expression of SSTR subtypes is associated with favorable prognosis, whereas COX2 overexpression is associated with poor prognosis in GEP-NETs. Taken together, COX2 could be a possible therapeutic target in some subsets of GEP-NETs.
Chromogranin A ; Cyclooxygenase 2 ; Humans ; Immunohistochemistry ; Liver ; Multivariate Analysis ; Neuroendocrine Tumors ; Prognosis ; Receptors, Somatostatin ; Retrospective Studies ; Somatostatin

PURPOSE: This study was undertaken to evaluate the significance of cyclooxygenase-2 (COX2) overexpression and the expression of somatostatin receptor (SSTR) subtypes in gastroenteropancreatic neuroendocrine tumors (GEP-NETs). MATERIALS AND METHODS: Two hundred and forty-seven cases of GEP-NET, comprising 86 foregut and 156 hindgut primary NETs, and 5 metastatic NETs in the liver, were studied retrospectively with immunohistochemistry for COX2, chromogranin A, Ki-67, SSTR1, SSTR2, and SSTR5. RESULTS: COX2 overexpression was observed in 54%(126 of 234), and SSTR1, SSTR2, and SSTR5 positivity in 84%(196 of 233), 72%(168 of 233), and 55%(128 of 232), respectively. COX2 overexpression was found to be positively correlated with Ki-67 labeling index and inversely correlated with the expression of SSTR subtypes. In addition, the expression of SSTR subtypes was tightly correlated in any comparative pairs. A significant inverse correlation was found between COX2 and SSTR2 expression in the foregut, but not hindgut NETs. Kaplan-Meier analyses showed that COX2 overexpression (p=0.003) and high Ki-67 labeling index (p<0.001) were associated with poor overall survival (OS), whereas expression of SSTR2 (p<0.001) was associated with better OS of GEP-NET patients. Multivariate analysis revealed negative SSTR2 expression as an independent prognostic marker in GEP-NET patients (p<0.001). CONCLUSION: Our results suggest that expression of SSTR subtypes is associated with favorable prognosis, whereas COX2 overexpression is associated with poor prognosis in GEP-NETs. Taken together, COX2 could be a possible therapeutic target in some subsets of GEP-NETs.
Chromogranin A ; Cyclooxygenase 2 ; Humans ; Immunohistochemistry ; Liver ; Multivariate Analysis ; Neuroendocrine Tumors ; Prognosis ; Receptors, Somatostatin ; Retrospective Studies ; Somatostatin

Primary carcinoid tumor of the kidney is a very rare disease. Until now, only 41 cases have been reported worldwide, and nine of these arose in a horseshoe kidney. In Korea, 3 cases have been reported to date, and all of these arose in a horseshoe kidney. We present a case of primary carcinoid tumor occurring in a normal kidney of a 45 year old man. A tumor was incidentally found close to the hilum of the left kidney. Histologically, the tumor exhibited trabecular and ribbon-like pattern of cuboidal or columnar cells. Mitotic activity was rarely seen. The tumor cells were positive for synaptophysin and chromogranin A. Numerous dense-core neurosecretary granules were observed by the electron microscopic examination. To our knowledge, the present case is the first report of primary renal carcinoid tumor arising in a normal kidney in Korea.
Carcinoid Tumor* ; Chromogranin A ; Humans ; Kidney* ; Korea ; Middle Aged ; Rare Diseases ; Synaptophysin

PURPOSE: Chromogranin A (CgA) has been considered to be valuable not only in the diagnosis but also in monitoring the disease response to treatment. However, only a few studies have been published on this issue. We purposed to evaluate whether biochemical response using plasma CgA level is reliable in concordance with the clinical response of grade 1-3 nonfunctiong gastroenteropancreatic neuroendocrine tumors (GEP-NETs). MATERIALS AND METHODS: Between March 2011 and September 2013, a total of 27 cases in 18 patients were analysed, clinically and radiologically while serial CgA tests were also conducted during treatment. Tumor responses were defined by both Response Evaluation Criteria in Solid Tumors (RECIST) criteria ver. 1.1 and biochemical criteria based on the CgA level. RESULTS: Among the 27 cases analysed, no difference in the basal CgA level was observed with regard to gender, primary tumor site, tumor grade (World Health Organization classification), liver metastasis, number of metastatic site, and line of chemotherapy. The overall response rate (RR) by RECIST criteria ver. 1.1 was six out of the 27 cases (22.2%) and eight out of the 27 cases (29.6%) for biochemical RR. The overall concordance rates of the response based on RECIST and biochemical criteria were 74%. In grades 1 and 2 GEP-NETs (n=17), the concordance rate of the disease control was 94.1%. There was a significant difference for progression-free survival (PFS) between responders and non-responder in accordance to biochemical criteria (35.73 months vs. 5.93 months, p=0.05). CONCLUSION: This study revealed that changes of the plasma CgA levels were associated with tumour response. Additionally, biochemical response based on serial CgA may be a predictive marker for PFS in GEP-NETs.
Chromogranin A* ; Diagnosis ; Disease-Free Survival ; Drug Therapy ; Humans ; Liver ; Neoplasm Metastasis ; Neuroendocrine Tumors* ; Plasma*