Higher World Health Organization Grade Research Articles

Reduced expression of the RNA-binding protein HuD in pancreatic neuroendocrine tumors correlates with low p27Kip1 levels and poor prognosis.

For the majority of patients diagnosed with pancreatic neuroendocrine tumors (NETs), there is significant malignant potential with a poor prognosis; however, the molecular abnormalities and pathogenesis of pancreatic NETs have not been firmly established. Here, we report that loss of expression of the RNA-binding protein HuD correlates with low p27Kip1 (p27) levels and poor prognosis in pancreatic NETs. HuD expression was frequently lost in many human pancreatic NETs, and these pancreatic NETs showed aggressive clinicopathological phenotypes with low p27 levels, increased tumor size, higher World Health Organization grade and pT stage of the tumor, and the presence of angioinvasion. Furthermore, loss of HuD was an independent, progression-free prognostic factor in multivariate survival analysis. However, the level of HuR, a member of the same Hu protein family as HuD, was not significantly correlated with pancreatic NET size and progression. Mechanistically, HuD enhanced p27 mRNA translation by interacting with both the 5'-untranslated region (UTR) and the 3'-UTR of p27 mRNA, and consequently suppressed cell cycle progression and tumor growth. In addition, HuD competed with miR-30a-3p for binding to the 3'-UTR of p27 mRNA, suggesting an interplay between HuD and miR-30a-3p in controlling p27 translation. Our results identify HuD as a pivotal suppressor of pancreatic NET growth, and suggest that HuD has potential value as a prognostic factor of pancreatic NETs. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Progesterone Receptor Is Responsible for Benign Biology of Skull Base Meningioma

Many studies have been performed to evaluate the roles of estrogen receptor and progesterone receptor (PGR) in meningiomas, but their influence on tumor behavior remains unclear. We retrospectively analyzed patients with meningioma who underwent surgical resection at our institute. Patients with data for immunohistochemical staining of estrogen receptor, PGR, and Ki-67 were included. The study included 161 patients comprising 61 skull base and 100 non-skull base meningiomas. Histologically, the number of patients with World Health Organization (WHO) grade I, II, and III disease were 132 (82.0%), 22 (14.7%), and 7 (4.4%), respectively. Tumor recurrence was observed in 21 (13.0%). Negative PGR, high Ki-67 index, incomplete resection, and WHO grade II or III were significantly correlated with tumor recurrence and shorter recurrence-free survival. Skull base meningiomas were difficult to remove entirely; 31 patients (50.8%) with skull base and 77 patients (77.0%) with non-skull base meningiomas had overall complete removal (P= 0.0006). Ki-67 indices, proportion of WHO grade II or III, and recurrence rate or recurrence-free survival did not differ between the tumor locations. The only difference was the proportion of patients with positive PGR, which was significantly higher for skull base meningiomas (61.5 ± 33.4% vs. 42.2 ± 35.7%, P= 0.0009). Although skull base meningiomas are often incompletely resected, there were no differences in recurrence-free survival or recurrence rate between skull base and non-skull base meningiomas. As the Ki-67 index and WHO grade were not different between these locations, the high rate of positive PGR may be responsible for the benign biology of skull base meningiomas.

NLRP3 in human glioma is correlated with increased WHO grade, and regulates cellular proliferation, apoptosis and metastasis via epithelial-mesenchymal transition and the PTEN/AKT signaling pathway.

Glioma is the most prevalent and fatal primary tumor of the central nervous system in adults, while the development of effective therapeutic strategies in clinical practice remain a challenge. Nucleotide-binding domain leucine-rich family pyrin-containing 3 (NLRP3) has been reported to be associated with tumorigenesis and progression; however, its expression and function in human glioma remain unclear. The present study was designed to explore the biological role and potential mechanism of NLRP3 in human glioma. The results demonstrated that overexpression of NLRP3, apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC), caspase-1 and interleukin (IL)-1β protein in human glioma tissues were significantly correlated with higher World Health Organization grades. The in vitro biological experiments demonstrated that NLRP3 downregulation significantly inhibited the proliferation, migration and invasion, and promoted the apoptosis of SHG44 and A172 glioma cell lines. Furthermore, western blot assays revealed that the downregulation of NLRP3 significantly reduced the expression of ASC, caspase-1 and IL-1β protein. Furthermore, NLRP3 knockdown caused the inhibition of epithelial-mesenchymal transition (EMT), and inhibited the phosphorylation of AKT serine/threonine kinase (AKT) and phosphorylation of phosphatase and tensin homolog (PTEN). Consistently, the upregulation of NLRP3 significantly increased the expression of ASC, caspase-1, IL-1β and phosphorylated-PTEN, promoted proliferation, migration, invasion and EMT, inhibited apoptosis, and activated the AKT signaling pathway. The data of the present study indicate that NLRP3 affects human glioma progression and metastasis through multiple pathways, including EMT and PTEN/AKT signaling pathway regulation, enhanced inflammasome activation, and undefined inflammasome-independent mechanisms. Understanding the biological effects of NLRP3 in human glioma and the underlying mechanisms may offer novel insights for the development of glioma clinical therapeutic strategies.

Spheno-Orbital Meningiomas: An Analysis Based on World Health Organization Classification and Ki-67 Proliferative Index.

To evaluate the clinical behavior of spheno-orbital meningiomas with regard to World Health Organization (WHO) tumor grade and Ki-67, a cellular marker of proliferation. A retrospective review over a 16-year period of the demographic, clinical, radiographic, and surgical data of all patients with spheno-orbital meningioma who underwent surgical resection. Tumor specimens were examined histologically using the current WHO 2016 classification and immunohistochemically using Ki-67/MIB-1 monoclonal antibody. Thirty-eight patients met all inclusion criteria: 78.9% of tumors were WHO grade I with a mean Ki-67 of 3.76, and 93% of patients were clinically stable at last follow up; 10.5% of lesions were WHO grade II (atypical) with a mean Ki-67 of 14.93, and 10.5% of lesions were WHO grade III (anaplastic) with a mean Ki-67 of 58.3. All grade II and III meningiomas exhibited an aggressive clinical course. There were statistically significant correlations between disease clinical progression and WHO tumor grade (p < 0.001), between disease clinical progression and Ki-67 (p < 0.001), and between increasing Ki-67 index and higher WHO grade (p < 0.001). For WHO grade I lesions, a Ki-67 of ≥3.3 correlated with recurrence (p = 0.0256). Overall, disease-specific mortality occurred in 5 (13%) patients. Ki-67 index is a valuable marker to use in conjunction with WHO grade to predict meningioma behavior, particularly in histologically borderline lesions, and possibly to identify a subset of WHO grade I tumors at risk of recurrence. This combination of methods can aid in tailoring treatment and surveillance strategies.

Aldehyde dehydrogenase 1 expression has prognostic significance in patients with glioma

As a cancer stem cell marker associated with tumorigenesis, aldehyde dehydrogenase 1 (ALDH1) has recently been identified in gliomas. However, an insufficient number of clinical studies have been published to demonstrate its prognostic significance in glioma. In the present study, a systematic meta-analysis was performed to comprehensively evaluate the correlation of ALDH1 with age, sex, the World Health Organization (WHO) grade, and overall survival (OS) in patients with glioma. A search of relevant publications was conducted to select eligible studies on this subject, and the pooled hazard ratios (HRs) and related risks (RRs) with 95% confidence intervals (95% CIs) were assessed. Publication bias was also evaluated using Begg's funnel plots. A total of 6 articles were identified that included a total of 1,057 patients. OS analysis revealed that a high expression of ALDH1 was significantly associated with poor 5-year OS (n=6; HR, 2.10; 95% CI, 1.13-3.91; P<0.0001), and a high WHO grade (III+IV; n=4; RR, 2.28; 95% CI, 1.31-3.99; P=0.001). In conclusion, a high expression of ALDH1 is associated with a high WHO grade of gliomas and a worse prognosis in patients with glioma. Further, well-designed clinical studies are required to confirm its role in the process of selecting a suitable therapeutic approach in glioma.

Meningiomas Adjacent to Major Venous Sinuses-Clinical Outcome and Recurrence.

Surgical treatment of meningiomas next to venous sinuses is difficult because of their irregular growth patterns and infiltration into the venous sinuses, making gross total resection impossible in some patients. We evaluated the postoperative clinical and neurologic course of this tumor subgroup. This study included 141 consecutive patients with meningioma located within 20 mm of a major venous sinus. Complete data sets were available for all patients. We reviewed patient charts and surgical reports for demographics, histology, and clinical and neurologic performance preoperatively and postoperatively and during follow-up. Radiographic images were screened for tumor extension, infiltration into the skull, sinus infiltration (Sindou grade), extent of resection (Simpson grade), and tumor recurrence. Immediate postoperative neurologic improvement was found in 53.7% (n= 36) of patients with preoperative neurologic deficits (n= 67). Follow-up was up to 13.5 years. Medical Research Council Neurological Performance Scale and Karnofsky performance scale postoperatively improved in 24.1% and 55.3% of patients, respectively. Local tumor recurrence was detected in 10.6% (n= 15) of patients. Higher World Health Organization grade (P= 0.03), tumor size (P= 0.001), and bone invasion (P=0.002) were predictors of local tumor recurrence. The median MIB-1 labeling index in patients with tumor recurrence was twice as high as in patients without recurrence. Surgical removal of meningiomas adjacent to venous sinuses reduces neurologic impairment and enables local tumor control in most patients. Tumor size, bone infiltration, and higher World Health Organization grade are important predictors of tumor recurrence.

RETRACTED: Downregulation of miR-204 expression correlates with poor clinical outcome of glioma patients

Glioma is the most common type of malignant neoplasm in the central nervous system, with high incidence and mortality rate. MicroRNAs, as a class of small noncoding RNAs, play an important role in carcinogenesis and correlate with glioma diagnosis and prognosis. In this study, we investigated the microRNA-204 (miR-204) concentration in glioma tissues and its relation to the expression of ezrin and bcl-2 mRNA, as well as its potential predictive and prognostic values in glioma. The concentrations of miR-204 were significantly lower in glioma tissues than in nontumor brain tissues and also were lower in high-grade than in low-grade gliomas (World Health Organization grades III and IV versus grades I and II). The miR-204 concentration was inversely correlated with the ezrin and bcl-2 concentrations. The miR-204 concentration was classified as high or low according to the median value, and low miR-204 correlated with higher World Health Organization grade, larger tumor, and worse Karnofsky performance score. Kaplan-Meier survival analysis demonstrated that patients with low miR-204 expression had shorter progression-free survival and overall survival than patients with high miR-204 expression. In addition, univariate and multivariate analyses showed that miR-204 expression was an independent prognostic feature of overall survival and progression-free survival. In conclusion, our study indicates that miR-204 is downregulated in glioma and may be a biomarker of poor prognosis in patients with this cancer.

Downregulation of miR-154 in human glioma and its clinicopathological and prognostic significance.

Objective MicroRNA-154 (miR-154) was previously reported to be downregulated in several types of human cancers and may act as a tumour suppressor. This study aimed to measure miR-154 levels and determine its clinical significance in human glioma.Methods This retrospective study analysed fresh human glioma specimens and non-neoplastic brain tissues using real-time quantitative reverse transcription–polymerase chain reaction to determine the relative levels of miR-154. The association between miR-154 levels and various clinicopathological characteristics and survival was analysed.Results A total of 115 patients with gliomas and 115 non-neoplastic brain tissues were examined. MiR-154 levels were significantly downregulated in gliomas compared with non-neoplastic brain tissues. Low levels of miR-154 were associated with high World Health Organization grade, large tumour size (≥ 5 cm), a low Karnofsky performance status score (< 80), and a shorter overall survival. Multivariate analyses using the Cox proportional hazards regression model confirmed that decreased miR-154 level was an independent predictor of a poor prognosis.Conclusions These results suggest that miR-154 downregulation may be involved in glioma formation and progression, and that miR-154 might serve as a potential prognostic biomarker for patients with this disease.

Roles of microRNA-99 family in human glioma.

ObjectiveDeregulation of microRNA (miR)-99 family members (miR-99a, miR-99b, and miR-100) has been reported to play a crucial role in many cancer types. However, their roles in human gliomas have not been fully elucidated. This study aimed to investigate the expression patterns of miR-99a, miR-99b, and miR-100 in glioma tissues and to evaluate their expression profiles with respect to tumor progression.MethodsQuantitative real-time polymerase chain reaction was performed to detect the expression levels of miR-99a, miR-99b, and miR-100 in glioma and matched non-neoplastic brain tissues. Then, the associations of their expression with various clinicopathological features of glioma patients were statistically analyzed. Moreover, the roles of miR-99a, miR-99b, and miR-100 in regulating glioma cell migration and invasion were determined via transwell assay in vitro.ResultsCompared with non-neoplastic brain tissues, miR-99a, miR-99b, and miR-100 expression levels were all significantly decreased in glioma tissues (all P<0.001). miR-99a-low, miR-99b-low, and miR-100-low expression more frequently occurred in glioma patients with low Karnofsky performance score (<90) and high World Health Organization grade (III–IV). Further functional experiments revealed that the enforced expression of miR-99a, miR-99b, and miR-100 resulted in the inhibition of cellular migration and invasion in glioma cells.ConclusionOur results strongly suggest that the aberrant expression of miR-99a, miR-99b, and miR-100 may be a common feature in human gliomas with aggressive clinicopathological features and may participate in malignant phenotypes of the tumors. These findings highlight the potential of the three miR-99 family members as novel therapeutic targets for human gliomas.

Upregulation of miR-183 expression and its clinical significance in human brain glioma.

Glioma is the most common type of primary malignant tumor in the central nervous system (CNS) with a high incidence and a high mortality rate, as well as an extremely low 5-year survival rate. As a class of small non-coding RNAs, microRNAs (miRNAs) may be closely involved in carcinogenesis and might also be connected with glioma diagnosis and prognosis. In this study, we aimed at investigating the expression level of microRNA-183 (miR-183) in 105 cases of glioma tissues of four World Health Organization (WHO) grades and 10 cases of normal brain tissues and its potential predictive and prognostic values in glioma. We found that the expression levels of miR-183 were significantly higher in glioma tissues than that in normal brain tissues, and also higher in high-grade gliomas (WHO grade III and IV) compared with low-grade gliomas (WHO grade I and II). The miR-183 expression level was classified as low or high according to the median value. High expression of miR-183 was found to significantly correlate with larger tumor size, higher WHO grade, and worse Karnofsky performance score (KPS). Kaplan-Meier survival analysis showed that patients with high miR-183 expression had worse overall survival (OS) and progression-free survival (PFS) than patients with low miR-183 expression. Moreover, univariate and multivariate analyses indicated that miR-183 expression level was an independent prognostic parameter of a patient's OS and PFS. In conclusion, our study indicated that miR-183 was upregulated in glioma, and that it may be used as a potential biomarker of poor prognosis in patients with glioma.

Clinicopathological and Prognostic Significance of CD133 in Glioma Patients: A Meta-Analysis.

In recent years, CD133 has been identified as a cancer stem cell (CSC) marker in gliomas. Nevertheless, the clinical and prognostic value of CD133 in glioma patients remains controversial. Therefore, we conducted a systematic meta-analysis to evaluate the correlation of CD133 with World Health Organization (WHO) grade, age, gender, overall survival (OS), and progression-free survival (PFS) in glioma patients. Eligible studies on this subject were included, and then pooled odd ratios (ORs) and hazard ratios (HRs) with 95 % confidence intervals (95 % CIs) were estimated. Publication bias was assessed by the funnel plots, and heterogeneity and sensitivity were analyzed as well. In the present study, 21 articles with the total number of 1535 patients were included. High expression of CD133 in glioma patients was associated with high WHO grade (III + IV) (n = 11, OR 5.10, 95 % CI 2.99-8.69; p = 0.000), rather than age (n = 4, OR 2.54, 95 % CI 0.68-9.52; p = 0.167) and gender (n = 4, OR 0.71, 95 % CI 0.21-2.45; p = 0.587). In addition, survival analysis demonstrated a significant association between CD133 high expression and poor 2-year OS (n = 11, HR 2.18, 95 % CI 1.29-3.7; p = 0.004), 5-year OS (n = 4, HR 10.39, 95 % CI 2.59-41.63; p = 0.001), as well as PFS (n = 10, HR 2.34, 95 % CI 1.62-3.37; p = 0.000). Taken together, this study suggests that CD133 expression correlates to higher grade of gliomas and worse prognosis in glioma patients. Thus, CD133 could be recommended as a useful pathological and prognostic biomarker in clinical practice.

Clinical and Prognostic Significances of Cytokeratin 19 and KIT Expression in Surgically Resectable Pancreatic Neuroendocrine Tumors.

Background:Pancreatic neuroendocrine tumors (PanNETs) are malignant endocrine neoplasms that present diverse clinical behaviors. Therefore, identification of biomarkers of PanNETs is important for stratification of the prognosis of PanNET patients. Recently, cytokeratin 19 (CK19) and KIT expression were reported to have prognostic significance in PanNET patients.Methods:To identify their prognostic significance, CK19 and KIT protein expression were assessed in 182 surgically resected PanNETs and compared with clinicopathologic factors.Results:Of 182 PanNETs cases, CK19 and KIT expression was noted in 97 (53.3%) and 16 (8.8%) cases, respectively. PanNET patients with CK19 expression had larger tumors (p=.006), higher World Health Organization (WHO) grade (p=.002) and pT classification (p<.001), increased distant metastasis (p=.004), and lymphovascular (p=.012) and perineural (p=.019) invasion. Similarly, those with KIT expression had larger tumors (p=.030), higher WHO grade (p=.001), advanced pT classification (p<.001), distant metastasis (p=.001), and lymphovascular invasion (p=.014). The 5-year survival rate for PanNET patients with KIT expression was significantly lower (62%) than that of patients without KIT expression (77%, p=.011), as determined by univariate but not by multivariate analyses.Conclusions:CK19 and KIT expression correlate with higher metastatic potential and advanced disease stage, and KIT expression is associated with worse survival in PanNET patients.

Prognostic Significance of Lactate/Proton Symporters MCT1, MCT4, and Their Chaperone CD147 Expressions in Urothelial Carcinoma of the Bladder

To investigate the prognostic significance of lactate/proton monocarboxylate transporters MCT1, MCT4, and their chaperone CD147 expressions in urothelial carcinoma of the bladder (UCB). We examined the expressions of MCT1, MCT4, and CD147 proteins in a total of 360 cases of UCB by immunohistochemistry. The immunohistochemical expressions were quantified using an ImageJ-based analysis program. MCT1, MCT4, and CD147 expressions were increased in 130 (36.1%), 168 (46.7%), and 228 (63.3%) UCB cases, respectively. Most tumor cells showed diffuse membranous staining, whereas normal urothelial cells showed negative or weak staining. High levels of MCT1 expression correlated with high World Health Organization grade (P<.001), advanced tumor node metastasis (TNM) stage (P<.001), nonpapillary growth type (P<.001), and lymphatic tumor invasion (P=.010), whereas high levels of MCT4 expression did not significantly correlate with any of these variables. High CD147 expression was associated with high World Health Organization grade (P<.001), advanced tumor node metastatis stage (P<.001), and nonpapillary growth type (P=.003). Univariate analyses revealed that high MCT1 (P<.001) and CD147 (P=.029) expressions were associated with poor overall survival and that high MCT4 expression was correlated with poor recurrence-free survival (P=.036). Multivariate analyses revealed that high MCT1 and MCT4 expressions were independent prognostic factors for poor overall survival and poor recurrence-free survival, respectively, in UCB patients. Our results indicate that increased MCT1, MCT4, and CD147 expressions have prognostic implications in UCB and suggest their roles in urothelial cancer metabolism.

Role of podocalyxin in astrocytoma: Clinicopathological and in vitro evidence

The present study examined the expression of podocalyxin (PODX) in surgically-resected astrocytomas, associated the levels of PODX expression with the clinicopathological characteristics and survival outcomes of astrocytoma and assessed how PODX affected the viability of astrocytoma cells following the administration of chemotherapeutic agents. The immunohistochemical analysis of 102 patient samples revealed that a high expression of PODX was significantly associated with high-grade astrocytomas (P<0.001) and a high Ki-67 labeling index (LI; P<0.001). A Kaplan-Meier survival analysis demonstrated that the high PODX expression group had significantly shorter disease-free survival (DFS) and overall survival (OS) rates compared with the low expression group (P<0.001). The multivariate analysis using the Cox’s proportional hazards model revealed that a high expression of PODX, a high World Health Organization grade and a high Ki-67 LI were independent factors for shorter DFS and OS times. A subsequent in vitro study using SW1783 and U-87 human astrocytoma cell lines revealed that knocking down PODX decreased astrocytoma cell viability against temozolomide-induced apoptotic stress through the inhibition of the Akt survival signaling pathway. In conclusion, the in vivo findings indicated that a high expression of PODX is predictive of a poor survival outcome and, thus, may be used as a prognostic factor to predict the survival outcomes of astrocytoma patients. The in vitro findings indicated that PODX may promote astrocytoma cell viability against chemotherapeutic agent-induced apoptotic stress through the Akt pathway, indicating that PODX may be a novel target for overcoming chemoresistance in astrocytomas.

Rosette-forming glioneuronal tumor of the fourth ventricle with neurocytoma component

Rosette-forming glioneuronal tumor (RGNT) was first published in 2002 and was described as a benign and indolent tumor. It was also included in the 2007 World Health Organization (WHO) classification of tumors as a grade 1 tumor for its benign clinical behavior and the possibility of surgical cure. Pathologically, RGNT is a mixed neuronal-glial tumor which consists of two distinct histological components-one with uniform neurocytes forming rosettes and/or perivascular pseudorosettes and the other being astrocytic in nature resembling pilocytic astrocytoma (biphasic pattern). We present the clinical course and pathological findings of two distinctively different cases. The first one was a 4-year-old girl with head trauma and a tumor which was incidentally found by CT. Pathology revealed that the tumor contained neurocytoma components and areas of relatively high proliferative ability with the first report of the presence of midsized bright elliptic cells. The other case was a 19-year-old girl whose imaging studies showed hydrocephalus and a brain stem tumor. She underwent endoscopic third ventriculostomy and biopsy, followed by observation. An MRI taken 6 months later showed progression of the tumor and she subsequently had the tumor excised. We are considering the possibility for our RGNT cases to correspond to a higher WHO grade as they have shown rapid progression, contrary to the already established, and their character, origin, differential diagnosis, and treatment plans have been discussed.

Higher World Health Organization grades of follicular lymphoma correlate with better outcome in two Nordic Lymphoma Group trials of rituximab without chemotherapy

A common treatment for follicular lymphoma is rituximab monotherapy. To identify patients for whom this regimen is adequate as first-line therapy, we applied the World Health Organization (WHO) classification for grading follicular lymphoma in a prospective central pathology review of the biopsies of previously untreated patients in two randomized trials of rituximab without chemotherapy. In the first trial (n1 = 53), higher WHO grades correlated with longer time to next treatment, independently of clinical prognostic factors (p = 0.030); the finding was replicated in the second trial (n2 = 221; p = 0.019). Higher grades were associated with better treatment responses (p = 0.018). Furthermore, also grades externally confirmed by independent local pathologists correlated with time to next treatment (p = 0.048). Flow cytometry in a separate patient series showed that the intensity of CD20 increased with the malignant cell size (p < 0.00005). In conclusion, WHO grade 1 follicular lymphoma correlates with inferior outcome after rituximab monotherapy. WHO grading might provide a clinically useful tool for personalized therapy.

Cortactin and Fascin-1 Correlate with WHO Grades in Primary Brain Tumors

Cortactin and fascin-1 play important roles in tumor progression and invasion in several human cancers, but not yet clarified in primary brain tumors. To test the possible role of these two markers in primary brain tumors, we performed immunohistochemical analysis of cortactin and fascin-1 in 65 meningiomas and 61 astrocytomas among various World Health Organization (WHO) grades. The immunostain intensity of these tumors was scored on a scale of 0 (absence of staining), 1 (weak staining), 2 (moderate staining), and 3 (strong staining). Additionally, the percentage of tumor staining was also scored 0 (less than 5%), 1 (5% to less than 25%), 2 (25% to less than 50%), 3 (50% to less than 75%) and 4 (75% to 100%). The percentage score was multiplied by the corresponding intensity score to obtain immunostain scores ranging from 0 to 12. Only scant (less than 5%) or undetectable cortactin and fascin-1 expression were demonstrated in 5 normal brain tissues. Higher cortactin and fascin-1 immunostain scores were significantly correlated with more advanced WHO grades of meningiomas (P=0.041 and P=0.047). In astrocytomas, higher WHO grade tumors was significantly associated with fascin-1 immunostain scores (P=0.045), but not with cortactin scores (P=0.461). In conclusion, overexpression of cortactin and fascin-1 may have some influence on tumor progression and invasion in meningiomas and astrocytomas.

CD74 expression is increased in high‐grade, invasive urothelial carcinoma of the bladder

This study aimed to identify the clinicopathological features of bladder cancer patients with high CD74 expression, as milatuzumab humanized anti-CD74 antibody is being evaluated in clinical trials for hematological malignancies. Expression of CD74 was examined in 342 urothelial carcinomas of the bladder, and two urothelial carcinoma cell lines by immunohistochemistry and western blotting, respectively. CD74 was overexpressed in 192 (56.1%) of the 342 cancer tissues, although it was not expressed in the cancer cell lines. CD74 staining was intense in tumor cells and inflammatory cells in the tumor stroma, but not in normal urothelium. CD74 expression was significantly associated with older age at diagnosis (≥ 68 years, P=0.048), high World Health Organization grade (P=0.019), advanced stages (P=0.001) and non-papillary growth pattern (P=0.040). CD74 expression was also correlated with the absence of tumor-infiltrating inflammatory cells (P<0.001) and the presence of tumor-associated inflammatory cells (P=0.017). However, CD74 expression was not related to recurrence-free and overall survivals in primary and subgroup analyses. In conclusion, urothelial bladder carcinomas with high CD74 expression are characterized by older age, high World Health Organization grade, non-papillary growth and advanced stages.

Clinical Significance and Prognostic Value of PAX3 Expression in Human Glioma

The paired box 3 (PAX3), a crucial transcription factor, is normally expressed during embryonic development and is absent in normal adult human tissues. Deregulated expression of PAX3 has been observed in tumors like rhabdomyosarcoma and melanomas. To assess deregulated PAX3 expression in patients with gliomas, these samples from 57 glioma patients (13 grade I, 16 grade II, 14 grade III, and 14 grade IV tumors) and 10 normal brain specimens acquired from 10 patients undergoing surgery for epilepsy as control were obtained. PAX3 expression was measured by RT-PCR, Western blot, and immunohistochemistry. Survival analyses were performed using the Kaplan-Meier method. Association between PAX3 expression, clinicopathological characteristics, and patients' survival were analyzed by using SPSS 17.0. We found that the expression of PAX3 was upregulated in high-grade glioma tissues compared with that in low-grade and normal brain tissues, and increased with ascending tumor World Health Organization (WHO) grades (P = 0.001). The increased PAX3 expression in gliomas was significantly associated with higher WHO grade (P = 0.021) and poorer disease-specific survival of patients (P = 0.001). Our results suggested that PAX3 might be an intrinsic regulator of progression in glioma cells and it might serve as a prognostic factor for this dismal disease.