Clinicopathological Significance, Related Molecular Changes and Tumor Immune Response Analysis of the Abnormal SWI/SNF Complex Subunit PBRM1 in Gastric Adenocarcinoma.

Background: PBRM1 gene abnormalities were recently found to play a role in tumor development and tumor immune activity. This article will explore the clinicopathological and molecular changes and tumor immune activity of the abnormal SWI/SNF complex subunit PBRM1 in gastric adenocarcinoma (GAC) and its significance. Methods: The cBioPortal, LinkedOmics and TISIDB datasets were used to analyze the abnormality of the PBRM1 gene in GAC and its relationship with prognosis, related molecular changes and tumor-infiltrating lymphocytes (TILs). In addition, 198 GAC cases were collected to further study the relationship between the loss/attenuation of PBRM1 expression and clinicopathology, prognosis, microsatellite stability, PD-L1 expression and TIL in GAC. DNA whole-exome sequencing was performed on 7 cases of gastric cancer with loss of PBRM1 expression. Results: The cBioPortal data showed that PBRM1 deletion/mutation accounted for 7.32% of GAC and was significantly associated with several molecular changes, such as molecular subtypes of GAC. The LinkedOmics dataset showed that PBRM1 mutation and its promoter DNA methylation showed lower PBRM1 mRNA expression, and PBRM1 mutation cases showed significantly higher mRNA expression of PD-L1 (CD274). TISIDB data showed that PBRM1 abnormalities were significantly positively associated with multiple TILs. In our group of 198 cases, the loss/attenuation of PBRM1 expression was significantly positively correlated with intra-tumoral tumor infiltrating lymphocytes (iTILs) and deficient MMR and PD-L1 expression. Kaplan-Meier survival analysis showed that the overall survival of GAC patients with loss/attenuation of PBRM1 expression was significantly better (p = 0.023). iTIL was an independent prognostic factor of GAC. Loss of PBRM1 expression often co-occurs with mutations in other SWI/SNF complex subunit genes, and there are some repetitive KEGG signaling changes. Conclusion: Abnormality of the PBRM1 gene may be related to the occurrence of some GACs and can affect tumor immune activity, thereby affecting clinicopathology and prognosis. It may be a potentially effective predictive marker for immunotherapy and a novel therapeutic approach associated with synthetic lethality.

CPNE1 Is a Useful Prognostic Marker and Is Associated with TNF Receptor-Associated Factor 2 (TRAF2) Expression in Prostate Cancer.

BACKGROUND CPNE1 plays a vital role in regulating cell differentiation. The clinical and biological values of CPNE1 in prostate cancer are still unclear. The aim of this study was to investigate the clinicopathological value of CPNE1 and the association of CPNE1 with TRAF2 expression in patients with prostate cancer. MATERIAL AND METHODS CPNE1 expression in prostate cancer was analyzed using Gene Expression Omnibus (GEO) databases. The Cancer Genome Atlas (TCGA) dataset was used to investigate the association of CPNE1 expression with TRAF2 expression in prostate cancer. The association of CPNE1 expression with recurrence-free survival in patients was also analyzed using the TCGA dataset. Immunohistochemistry assay was performed to examine CPNE1 expression in 65 normal prostate samples and 114 prostate cancer samples. The recurrence-free survival in patients was evaluated using Kaplan-Meier curves and log-rank test. In addition, multivariate and univariate analyses of prognostic factors were investigated by Cox regression. The effect of CPNE1 on TRAF2 expression was explored in human prostate cancer DU-145 cells. RESULTS Our results showed that expression level of CPNE1 is higher in prostate cancer than in normal prostate tissues (P=0.006). In the GSE35988 dataset, CPNE1 expression was found to be upregulated in castration-resistant prostate cancer compared with non-castration-resistant prostate cancer (P<0.001). Furthermore, we found that CPNE1 high expression was significantly related to tumor stage, Gleason score, and poorer biochemical recurrence-free survival in prostate cancer patients. Co-expression analysis of TCGA data showed that CPNE1 is significantly associated with TRAF2 expression. CPNE1 overexpression can upregulate TRAF2 expression in prostate cancer DU-145 cells as determined by Western blotting and immunofluorescence assays. CONCLUSIONS Overall, our findings suggest that CPNE1 is a valuable prognostic marker for evaluating recurrence-free survival and is positively related to TRAF2 expression in prostate cancer.

TRAF2 is a Valuable Prognostic Biomarker in Patients with Prostate Cancer.

BACKGROUND TRAF2 exerts important functions in regulating the development and progression of cancer. The aim of this study is to investigate whether TRAF2 is a valuable prognostic biomarker and to determine if it regulates TRAIL-induced apoptosis in prostate cancer. MATERIAL AND METHODS Microarray gene expression data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used to determine TRAF2 expression in prostate cancer. TRAF2 expression in prostate cancer was further investigated by immunohistochemistry assay. Kaplan-Meier curves and log-rank test were used to assess the recurrence-free rate. Cox regression was used to analyze prognostic factors. Effects of TRAF2 on regulating TRAIL-induced apoptosis in DU-145 cells were further investigated. RESULTS We found that TRAF2 was significantly upregulated in prostate cancer compared with normal prostate samples (P<0.001). In addition, compared with primary prostate cancer, TRAF2 was upregulated in metastatic prostate cancer (P=0.006). Furthermore, our results showed that high expression of TRAF2 was significantly associated with tumor stage of prostate cancer (P=0.035). TRAF2 high expression was associated with poorer recurrence-free survival in prostate cancer patients (P=0.013). TRAF2 was found to be a valuable independent prognostic factor for predicting recurrence-free survival (P=0.026). In addition, the present results indicate that TRAF2 affects TRAIL-induced apoptosis in prostate cancer DU-145 cells via regulating cleaved Caspase-8 and c-Flip expression. CONCLUSIONS TRAF2 could be a novel prognostic biomarker for predicting recurrence-free survival in patients with prostate cancer, which might be associated with the effects of TRAF2 in regulating TRAIL-induced apoptosis in prostate cancer cells via c-Flip/Caspase-8 signalling.

Analysis of the age of Panax ginseng based on telomere length and telomerase activity.

Ginseng, which is the root of Panax ginseng (Araliaceae), has been used in Oriental medicine as a stimulant and dietary supplement for more than 7,000 years. Older ginseng plants are substantially more medically potent, but ginseng age can be simulated using unscrupulous cultivation practices. Telomeres progressively shorten with each cell division until they reach a critical length, at which point cells enter replicative senescence. However, in some cells, telomerase maintains telomere length. In this study, to determine whether telomere length reflects ginseng age and which tissue is best for such an analysis, we examined telomerase activity in the main roots, leaves, stems, secondary roots and seeds of ginseng plants of known age. Telomere length in the main root (approximately 1 cm below the rhizome) was found to be the best indicator of age. Telomeric terminal restriction fragment (TRF) lengths, which are indicators of telomere length, were determined for the main roots of plants of different ages through Southern hybridization analysis. Telomere length was shown to be positively correlated with plant age, and a simple mathematical model was formulated to describe the relationship between telomere length and age for P. ginseng.

Cripto-1 expression and its prognostic value in human bladder cancer patients.

Cripto-1 is an important embryonic gene that involved in self-renewal and maintenance of pluripotency of stem cells. Overexpression of Cripto-1 has been found to be correlated with tumorigenesis and may affect tumor recurrence and metastasis. The previous studies indicate that Cripto-1 might be a potential prognostic biomarker for several malignancies. The aim of this study is to examine Cripto-1 expression pattern and clinicopathological significance in human bladder cancer patients. We investigated Cripto-1 expression in 30 paired bladder cancer tissues and corresponding noncancerous bladder tissues using real-time quantitative RT-PCR (qRT-PCR). Moreover, Cripto-1 expression in 130 bladder cancer specimens and bladder cancer T24 and 5637 cells were analyzed using immunohistochemistry and immunofluorescence assays. The recurrence/metastasis-free survival was assessed by Kaplan-Meier method and log-rank test. Cox regression was also used for univariate and multivariate analyses of prognostic factors. The results showed that Cripto-1 expression is increased in bladder cancer tissues and is significantly associated with tumor size (P = 0.005) and tumor grade (P = 0.035). In addition, the expression level of Cripto-1 in bladder cancer was also found to be significantly associated with SRY-related HMG-box gene 2 expression (P = 0.003) and Ki-67 (P = 0.001). Compared with the patients with low Cripto-1 expression, the patients with high Cripto-1 expression had significantly poorer recurrence/metastasis-free survival (P = 0.011). Cox regression showed that Cripto-1 might be an independent prognostic factor for recurrence/metastasis-free survival (P = 0.036). Our findings suggest that high Cripto-1 expression might be involved in the development of bladder cancer and a potentially effective prognostic marker in bladder cancer patients.

Expression of amyloid-ß protein and amyloid-ß precursor protein after primary brain-stem injury in rats.

Amyloid-ß (Aß) protein and its precursor, amyloid-ß precursor protein (ß-APP), have traditionally been used in the diagnosis of Alzheimer disease. Their use in diagnosis of traumatic brain injury by forensic analysis is becoming more widespread. However, to date, no reliable small animal model exists to evaluate these brain injury indicators. To address this, we have studied primary brain-stem injury in rats to assess the appearance of diffuse axonal injury in brain sections and correlate these findings with appearance of Aß and relative ß-APP mRNA levels. Using an EnVision 2-step immunohistochemical staining method to measure axon diameter, we found that there was significant difference in axon diameters within the medulla oblongata and several time points after brain injury, ranging from 3 to 24 hours. In addition, mRNA expression levels of ß-APP increased following brain injury, peaking 3 hours following injury and decreasing back to baseline levels by 24 hours after injury. These results suggest that using immunohistochemistry and reverse transcription-polymerase chain reaction to detect changes in Aß-associated axonal changes and ß-APP mRNA levels, respectively, can be useful for the diagnosis of diffuse axonal injury during autopsy at early time points following fatal brain injury.

Predictive value of Sox2 expression in transurethral resection specimens in patients with T1 bladder cancer.

Sox2 is thought to be an important regulator of self-renewal in embryonic stem cell. According to the cancer stem cell (CSC) theory, the overexpression of Sox2 is potentially involved in carcinogenesis and could affect tumor recurrence and metastasis. Previous study proved Sox2 might be prognostic marker for multiple human malignancies. The purpose of this study was to investigate the clinicopathological significance of Sox2 expression in human non-muscle-invasive bladder cancer. We examined Sox2 expression in 32 paired non-muscle-invasive bladder cancer tissues and adjacent non-cancerous tissues by quantitative real-time RT-PCR (qrtRT-PCR). In addition, we analyzed Sox2 and Ki-67 expression in 126 non-muscle-invasive bladder cancer samples and bladder cancer cell line T24 by immunohistochemistry and immunofluorescence assays. The recurrence-free survival was determined by Kaplan-Meier method and log-rank test. Cox regression was adopted for univariate and multivariate analyses of prognostic factors. The expression of Sox2 was significantly increased in non-muscle-invasive bladder cancer tissues. Sox2 expression was significantly correlated with that of Ki-67 (P < 0.001). The expression of Sox2 was significantly associated with tumor size (P = 0.006), tumor number (P = 0.037), and tumor grade (P < 0.001). Patients with high Sox2 expression had significantly poorer recurrence-free survival (P = 0.0002) when compared with patients with the low expression of Sox2. On multivariate analysis, Sox2 expression and tumor grade were found to be independent prognostic factors for recurrence-free survival (P < 0.05). Our data suggested for the first time that the high expression of Sox2 may contribute to the development of non-muscle-invasive bladder cancer and serve as a novel prognostic marker in patients with T1 bladder cancer.

Sinonasal teratocarcinosarcoma: a clinical and pathological analysis.

The goal of this study was to assess the pathological and differential diagnoses of sinonasal teratocarcinosarcoma (SNTCS) in order to ultimately improve the diagnosis and treatment of this rare disease. Data from 2 cases of sinonasal teratocarcinosarcoma from the Wuxi People's Hospital (China) were analyzed. The clinical presentation for these patients consisted of nasal obstruction, epistaxis, and headache. On further physical examination, the presence of a polypoid mass was identified and, despite surgery and radiotherapy, both cases experienced recurrence. Histologically, the tumors showed a heterogeneous mixture of components from the 3 germ layers, primitive neuroepithelial elements, diagnostic immature squamous cell nests (clear cell nests), and various epithelial and mesenchymal components. Staining of the different germ layers corresponded with the appropriate immune markers. In case 1, the postradiotherapy resection specimen was completely dominated by a mature teratoma, with a complete absence of the corresponding adenocarcinoma and fibrosarcoma components. To date, this is the first study describing this composition within an SNTCS recurrent tumor. In summary, SNTCS is a rare tumor characterized by the presence of benign and malignant epithelial, mesenchymal, and dysembryomal components. Owing to its heterogeneous histologic appearance, adequate sampling and recognition of all SNTCS components are needed for future diagnosis. Currently, surgical removal, postoperative radiotherapy, and a histology-specific multidrug chemotherapy appear to be the best therapeutic approach. Future individualized therapy may also hold promise.

[Clinicopathological analysis of sudden cardiac death cases by autopsy].

OBJECTIVE: To explore the major correlation factors and cardiac pathological changes of sudden cardiac death (SCD). METHODS: The clinical and pathological profiles of 119 SCD cases at Wuxi People's Hospital Affiliated to Nanjing Medical University from January 1985 to March 2012 were retrospectively analyzed. And the parameters of gender, age, causes of death and pathological changes of SCD were included. RESULTS: Among them, the primary etiologies were coronary atherosclerotic heart disease (n = 53, 44.5%), hypertensive heart disease (n = 9, 7.6%), myocarditis (n = 13, 10.9%), acute pulmonary embolism (n = 8, 6.7%) and myocardiopathy(n = 3, 2.5%). The heart weights of male and female cases were (407 ± 126) and (349 ± 101) g respectively. Among 53 cases of coronary heart disease, there were 28 cases (52.8%) of grade IV coronary artery atherosclerotic stenosis and 17 were involved with multiple branches. The differences of coronary artery stenosis were insignificant between gender and age (P > 0.05). Acute myocardial infarction occurred in 18 cases and 15 of them were complicated with old myocardial infarction (OMI) while there were 27 cases of simple OMI. Twenty cases (16.8%) without obvious cardiac organic pathological changes were classified as juvenile sudden unexplained death. CONCLUSIONS: Sudden and dangerous SCD frequently occurs in elders. Multiple severe coronary atherosclerotic stenosis is an important pathological hallmark of SCD.

Interdigitating dendritic cell tumor of the lymph node in the right submaxillary region: a case report and review of the literature.

Interdigitating dendritic cell tumor/sarcoma is an extremely rare neoplasm that mainly occurs in the lymph node, with only 51 cases reported in the literature to date. The authors report the case of a 41-year-old woman who presented with a 4-month history of a gradually enlarging painless mobile lymphadenopathy in the right submaxillary region. The lymph node mass was completely resected and was treated with 1 cycle of CHOP chemotherapy. After 10 months, she was alive with no evidence of disease. Because interdigitating dendritic cell sarcomas are rare and can show morphologic and immunohistochemical heterogeneity, correct diagnosis requires a high index of suspicion and complete pathological study.

Giant-cell anaplastic carcinoma with osteoclastic giant cells of the chest cavity: a distinctive form of thymic carcinoma?

Here, the authors describe a case of giant-cell anaplastic carcinoma with osteoclastic giant cells of the chest cavity-which could be a distinctive form of thymic carcinoma-which expressed CD5 and CD45. To the authors' knowledge, there has been no previous report on this subject. A 62-year-old woman presented with continuous pain in the left back associated with coughing and shortness of breath for more than 2 months prior to referral to the hospital. Palliative resection of a mediastinal tumor was performed. During the operation, it was found that the mass occupied most of the chest invading the chest wall, aorta, vena cava, and lung tissue. The patient soon died from diabetic complications in spite of anti-infection treatment. The tumor was composed of large areas of necrosis and anaplastic neoplastic giant cells with high mitotic activity, and osteoclast-like cells; there was marked inflammatory cell infiltration. The anaplastic neoplastic giant cells were immunoreactive for CKpan, CD5, CD45, VIM, and p53. Approximately 50% to 60% of the tumor cells showed immunoreactivity for Ki-67. In situ hybridization for Epstein-Barr virus-encoded RNA was negative for tumor cells and nonneoplastic osteoclastic giant cells. Because this tumor is very rare, extensive clinical, radiological, and morphological examinations as well as immunohistochemical studies are essential to make the diagnosis.

[Pathologic and immunohistochemical study on lethal primary brain stem injury].

OBJECTIVE: To study the histopathologic changes of primary brain stem injury and to investigate their significance in the diagnosis of primary brain stem injury. METHODS: Sixty-five autopsy cases died of primary brain stem injury and other diseases were enrolled into this study. The cases were subdivided into brain stem injury group (n = 25) and control group (including 20 cases died of cardiovascular disease and 20 cases died of non-cardiovascular diseases). The brain stem tissue sections were stained with hematoxylin-eosin and silver impregnation techniques. Immunohisto chemical study for glial fibrillary acidic protein, neurofilament, amyloid-beta and myelin basic protein was carried out. The widest cross diameters of 10 axons highlighted by immunostaining were measured in each low power field (x 100) through light miscroscopy in all the cases studied. RESULTS: In comparing with that of the control group, there were differences in the degree of contusion lesion, reactive astrocytosis, edema and pathologic changes of neuronal cells present in the brain stem injury group and was statistically significant (P < 0.05). The axons locating in the brain stem injury group showed a distinctive histology by the appearance of significantly larger diameters (P < 0.05). CONCLUSIONS: Primary brain stem injury demonstrates certain distinctive histopathologic changes and measurement of axonal diameters provides an additional quantitative index useful in autopsy diagnosis.