We aimed to investigate the prognostic value of chromogranin A (CgA) in castration-resistant prostate cancer (CRPC). We conducted a systematic literature search of PubMed, Web of Science, and EMBASE for citations published prior to September 2017 that described CgA and CRPC and performed a standard meta-analysis on survival outcomes. Our meta-analysis included eight eligible studies with 686 patients. The results were as follows: progression-free survival (PFS) was associated with CgA level (hazard ratio [HR] = 2.47, 95% confidence interval [CI]: 1.47-4.14, P = 0.0006); PFS was relative to CgA change (HR = 9.22, 95% CI: 3.03-28.05, P < 0.0001); and overall survival (OS) was relative to CgA level (HR = 1.47, 95% CI: 1.15-1.87, P = 0.002). When we divided the patients into two groups according to therapy status, the result for OS relative to CgA level was an HR of 1.26 (95% CI: 1.09-1.45, P = 0.001) in the first-line hormonal therapy group, and an HR of 2.33 (95% CI: 1.40-3.89, P = 0.001) in the second-line hormonal therapy or chemotherapy group. This meta-analysis indicated that a high CgA level had a negative influence on OS and PFS in CRPC patients. In addition, CRPC patients with a rising CgA had a shorter PFS. Further studies are needed to verify the prognostic value of CgA in CRPC.
Chromogranin A/analysis* ; Humans ; Male ; Predictive Value of Tests ; Prognosis ; Prostatic Neoplasms, Castration-Resistant/diagnosis* ; Reproducibility of Results ; Survival Analysis

OBJECTIVETo evaluate the stress level during parachuting training by salivary biomarker and to study the dynamic characteristics.

METHODSTwenty recruits of military parachuting training completed 8 trainings in a month. The saliva samples were collected at 2 h and 1h before boarding and at 0.5 h after landing on the 1st, 4th and 7th trainings. The levels of cortisol, chromogranin A and α-amylase in saliva samples were detected.

RESULTSThe concentrations of cortisol, chromogranin A and activity of α-amylase increased significantly from pre-boarding to landing during 3 trainings. The concentrations of cortisol, chromogranin A and activity of α-amylase at 2 h before boarding and at 0.5 h after landing decreased significantly with the training times. However, the changes of 3 biomarkers at 1 h before boarding among 3 trainings were not significant.

CONCLUSIONThe levels of stress increased significantly for 20 recruits from pre-boarding to landing during parachuting trainings. The stress levels of 20 recruits before boarding and after landing significantly decreased with parachuting training times.

Aviation ; Biomarkers ; analysis ; Chromogranin A ; analysis ; Humans ; Hydrocortisone ; analysis ; Male ; Saliva ; chemistry ; Stress, Psychological ; Young Adult ; alpha-Amylases ; analysis

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

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

OBJECTIVETo discuss the diagnosis and treatment of primary hepatic carcinoid tumor (PHCT).

METHODSReport one case of huge PHCT treated in February 2004, and search the other 19 cases which were published from January 1994 to December 2006 in the Chinese biological and medical literature database. The clinical manifestation, pathological findings, diagnosis and treatment of these 20 PHCT patients were analyzed retrospectively.

RESULTSThe main symptoms were abdominal pain or discomfort (8 cases) and abdominal mass (7 cases), cases with typical carcinoid syndrome were rare (3 cases). Immunohistochemical staining was positive for neuron-specific enolase, chromogranin A and synaptophysin in most cases. Sixteen cases received operation, among which there were 13 removed completely, other 4 cases were treated by transcatheter arterial chemoembolization (TACE).

CONCLUSIONSThe definite diagnosis of PHCT depends on pathological and histochemical findings. Complete surgical resection is the best treatment for PHCT with favourable prognosis. TACE is also effective for nonoperative cases.

Antigens, CD34 ; analysis ; Carcinoid Tumor ; diagnosis ; metabolism ; therapy ; Chromogranin A ; analysis ; Diagnosis, Differential ; Humans ; Immunohistochemistry ; Liver Neoplasms ; diagnosis ; metabolism ; therapy ; Male ; Middle Aged

BACKGROUND/AIMS: Colorectal neuroendocrine carcinoma is a rare neoplasm exhibiting fulminant progression and having poor prognosis. The purpose of this study is to verify the clinicopathologic characteristics of colorectal neuroendocrine carcinoma. METHODS: From June 1997 to December 2004 at Asan Medical Center, ten patients were originally identified as colorectal neuroendocrine carcinoma on the basis of H&E and immunohistochemical staining (IHC). Carcinoid tumors were excluded in this study. Medical records of thirteen patients were reviewed retrospectively. RESULTS: Ten patients (0.2%) with colorectal neuroendocrine tumors were identified from 4,512 patients with colorectal cancer; ten neuroendocrine carcinomas and three adenocarcinomas with neuroendocrine differentiation. Their median age was 60 (41-83) years. The subjects consisted of six males and seven females. Nine tumors were located in the rectum, two in the sigmoid, and each one in the transverse colon and cecum, respectively. Nine of ten neuroendocrine carcinomas expressed synaptophysin, but chromogranin A were expressed in four. All patients were advanced at the time of diagnosis, with AJCC TNM staging: stage IIIB (n=2), stage IIIC (n=3), and stage IV (n=8). The median survival for ten neuroendocrine carcinomas and three adenocarcinomas with neuroendocrine differentiation were 16.4 months and 30 months, respectively. Five patients who received chemotherapy showed median survival of 32 months (stage III) and 17.5 months (stage IV), whereas other five patients without chemotherapy died with a median survival of 6.2 months. CONCLUSIONS: Colorectal neuroendocrine tumors are extremely rare showing aggressive behavior biologically, i.e fulminant early distant metastasis. Nevertheless, improved survival may be achieved by aggressive multimodality therapy.
Adenocarcinoma/pathology ; Adult ; Aged ; Aged, 80 and over ; Biopsy ; Carcinoma, Neuroendocrine/drug therapy/mortality/*pathology ; Chromogranin A/analysis/immunology ; Colorectal Neoplasms/drug therapy/mortality/*pathology ; Drug Therapy, Combination ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Metastasis ; Retrospective Studies ; Sigmoid Neoplasms/drug therapy/mortality/pathology ; Synaptophysin/analysis/immunology ; Tumor Markers, Biological/analysis/immunology

OBJECTIVETo describe the morphologic features and immunohistochemistry of spindle cell carcinoma of breast with neuroendocrine differentiation.

METHODSRetrospective review of 2500 cases of breast carcinoma showed 5 cases (0.2%) with a predominance (> 80%) of spindle cell component. Amongst the 5 cases studied, 2 represented intraductal spindle cell carcinoma and 3 represented invasive spindle cell carcinoma. The paraffin sections were stained with hematoxylin and eosin, alcian blue, periodic acid-Schiff and reticulin stain. Immunohistochemical studies for AE1/AE3, CEA, EMA, CK7, 34betaE12, NSE, synaptophysin, chromogranin A, Leu-7, vimentin, S-100, SMA, calponin, estrogen receptor, progesterone receptor, c-erbB2, E-cadherin, Ki-67 and p53 were also carried out. Follow-up information was available in 4 of the 5 cases.

RESULTSThe mean age of the patients was 68 years. Histologically, all tumors were predominantly composed of elongated spindle cells. Three of these cases also contained tumor cells with vacuolated cytoplasm, alcian blue-positive tumor cells were observed in 4 cases. Immunohistochemically, the spindle tumor cells in all cases expressed AE1/AE3, CEA, EMA, E-cadherin and synaptophysin. CK7 was positive in 4 cases, NSE in 3 cases, chromogranin A and Leu-7 in 2 cases. Estrogen receptor was expressed in 4 cases and progesterone receptor in 2 cases. Overexpression of c-erbB2 oncoprotein was detected in only 1 case. Vimentin was focally positive in 1 case. Two cases of intraductal spindle cell carcinoma and 1 of the 3 cases of invasive spindle cell carcinoma were classified as neuroendocrine carcinoma of spindle cell type, while the remaining 2 cases of invasive spindle cell carcinoma were considered as metaplastic carcinoma with neuroendocrine differentiation. Amongst the 4 patients with follow-up information available, 3 were still alive 24 to 58 months after the initial diagnosis. One patient died within 27 months of diagnosis.

CONCLUSIONSThe presence of spindle tumor cells and sometimes intracytoplasmic mucin are useful morphologic clues in diagnosing spindle cell carcinoma of the breast with neuroendocrine differentiation. Intraductal neuroendocrine spindle cell carcinoma needs to be distinguished from usual ductal hyperplasia and intraductal papilloma. On the other hand, invasive spindle cell carcinoma with neuroendocrine differentiation needs to be distinguished from spindle cell myoepithelioma, malignant melanoma and sometimes soft tissue neoplasm.

Aged ; Biomarkers, Tumor ; analysis ; Breast Neoplasms ; chemistry ; pathology ; Carcinoma ; chemistry ; pathology ; Carcinoma, Intraductal, Noninfiltrating ; chemistry ; pathology ; Chromogranin A ; Chromogranins ; analysis ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neuroendocrine Tumors ; chemistry ; pathology ; Phosphopyruvate Hydratase ; analysis ; Retrospective Studies ; Synaptophysin ; analysis

BACKGROUND/AIMS: p53 is known to play a central role in sensing and signaling for the growth arrest and apoptosis in cells with DNA damage. Mutation of p53 is a frequent event in esophageal squamous cell carcinoma (ESCC). p16 protein binds to cyclin dependent kinase 4 (CDK4) inhibiting the ability of CDK4 to interact with cyclin D1, and stimulates the passage through the G1 phase of cell cycle. We observed the expression patterns and frequencies of p53, p16, and cyclin D1 in esophageal dysplasia and in esophageal squamous cell carcinomas. METHODS: In 15 patients of ESCC, 5 patients of esophageal dysplasia and 5 volunteers with normal esophagus, tissue specimens were taken from esophageal lesions during the operation or endoscopic examination. We used specific monoclonal antibodies for p53 protein, p16INK4 protein and cyclin D1. Immunoreactivity was scored. RESULTS: Mean age of all groups was 66 years old (range 47-93) and men to women ratio was 19:1. p53 mutation was observed in 87% (13/15) of ESCC, in 80% (4/5) of esophageal dysplasia, in 0% (0/5) of normal mucosa (p=0.001). p16 expression was seen in 40% (2/5) of esophageal dysplasia, 27% (4/15) of ESCC and 100% (5/5) of normal mucosa (p=0.016). Cyclin D1 expression was not significantly different among 20% (1/5) of esophageal dysplasia, 53% (8/15) of ESCC and 20% (1/5) of normal mucosa. Either the expression of p53 mutation or the loss of p16 occurred in 80% (4/5) of esophageal dysplasia and in 93% (14/15) of ESCC. CONCLUSIONS: The expression of p53 mutation and the loss of p16 might play a central role in the pathogenesis of esophageal squamous cell carcinoma (ESCC), and contribute to the development of precancerous lesion such as dysplasia. In addition, there is a possibility that the mutations of p53 and p16 silencing would be the early events in ESCC development.
Aged ; Carcinoma, Neuroendocrine/*diagnosis/pathology ; Chromogranin A/analysis/immunology ; Drainage ; Female ; Humans ; Immunohistochemistry ; Liver Abscess/*radiography/surgery ; Liver Neoplasms/*diagnosis/pathology ; Radiography, Abdominal ; Synaptophysin/analysis/immunology ; Tomography, X-Ray Computed

OBJECTIVETo study the impact of short-term neoadjuvant hormonal treatment on neuroendocrine (NE) differentiation and the relation of NE differentiation and tumor regression.

METHODSThe radical prostatectomy specimens and the biopsy specimens of the same 18 patients with prostate cancer were compared. The effect of hormonal treatment on NE-differentiation was evaluated by specific antibodies against chromogranin A (ChA) and serotonin (5-HT).

RESULTSThe ChA-positive cell count was 3.2 x 10(-5)/microm(2) [(0-5.7) x 10(-5)/microm(2)] before hormonal treatment and 2.3 x 10(-5) microm(2)[(0-6.6) x 10(-5)/microm(2)] afterward (P > 0.05). For the proportion of NE-positive tumor, it was 7.0% (0%-14.9%) and 4.5% (0%-13.1%) (P > 0.05). No correlation existed between NE-differentiation and the neoadjuvant hormonal treatment. The NE cell density did not differ significantly between 12 non-/slightly regressive tumor foci and 6 highly regressive ones (P > 0.05).

CONCLUSIONShort-term neoadjuvant hormonal therapy does not induce clonal propagation of NE cells. The degree of tumor regression following short-term neoadjuvant hormonal therapy is not correlated with the NE differentiation.

Aged ; Androgen Antagonists ; therapeutic use ; Antineoplastic Agents, Hormonal ; therapeutic use ; Chromogranin A ; Chromogranins ; analysis ; Humans ; Male ; Middle Aged ; Neoadjuvant Therapy ; Neurosecretory Systems ; pathology ; Prostatic Neoplasms ; drug therapy ; pathology ; Serotonin ; analysis