HuR Protein in Hepatocellular Carcinoma: Implications in Development, Prognosis and Treatment.

Hu-antigen R (HuR) is a post-transcriptional regulator that belongs to the embryonic lethal abnormal vision Drosophila-like family (ELAV). HuR regulates the stability, translation, subcellular localization, and degradation of several target mRNAs, which are implicated in carcinogenesis and could affect therapeutic options. HuR protein is consistently highly expressed in hepatocellular carcinoma (HCC) compared to the adjacent normal liver tissue and is involved in the post-transcriptional regulation of various genes implicated in liver malignant transformation. Additionally, HuR protein seems to be a putative prognosticator in HCC, predicting worse survival. This review summarizes the recent evidence regarding the role of HuR in primary liver tumors, as presented in clinical studies, in vitro experiments and in vivo animal models. In conclusion, our review supports the consistent role of HuR protein in the development, prognosis, and treatment of HCC. Additional studies are expected to expand current information and exploit its putative employment as a future candidate for more personalized treatment in these tumors.

Elevated Hu-Antigen Receptor (HuR) Expression is Associated with Tumor Aggressiveness and Poor Prognosis but not with COX-2 Expression in Invasive Breast Carcinoma Patients.

Hu-antigen R (HuR), a RNA-binding protein, is considered to play a crucial role in tumor development and progression by stabilizing or regulating a group of cellular mRNAs of cancer-related genes, such as cyclooxygenase-2 (COX-2). The present study aimed to evaluate the clinical significance of HuR and COX-2 expression in invasive breast carcinoma. HuR and COX-2 protein expression was assessed immunohistochemically on paraffin-embedded breast cancer tissue sections obtained from 121 patients and was statistically analyzed with clinicopathological parameters, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), as well as with tumor cells' proliferative capacity and overall and disease-free patients' survival. High HuR expression was positively associated with larger tumor size and advanced disease stage (p = 0.0234 and p = 0.0361, respectively), being more frequently observed in ER negative cases (p = 0.0208). High COX-2 expression was negatively associated with histological (p < 0.0001) and nuclear (p = 0.0033) grade and tumor cells' proliferative rate (p = 0.0015), being more frequently observed in luminal-A compared to other molecular subtypes (p = 0.0221). High HuR expression was associated with poor overall and disease-free patients' survival at both univariate (log-rank test, p = 0.0092 and p = 0.0004, respectively) and multivariate (Cox-regression analysis, p = 0.0223 and p = 0.0004, respectively) level. On the other hand, high COX-2 expression was associated with favorable overall and disease-free patients' survival merely at univariate level (log-rank test, p = 0.0389 and p = 0.0154, respectively). HuR expression was not associated with COX-2 expression (Spearman R = 0.1489, p = 0.1032). The present data support evidence that HuR is associated with tumor aggressiveness and poor prognosis in breast carcinoma, reinforcing its potential as promising therapeutic target in this type of neoplasia.

Histone deacetylase (HDAC)-1, -2, -4 and -6 expression in human pancreatic adenocarcinoma: associations with clinicopathological parameters, tumor proliferative capacity and patients' survival.

BACKGROUND: Histone deacetylases (HDACs) have been associated with malignant tumor development and progression in humans. HDAC inhibitors (HDACIs) are currently being explored as anti-cancer agents in clinical trials. The present study aimed to evaluate the clinical significance of HDAC-1, -2, -4 and -6 protein expression in pancreatic adenocarcinoma. METHODS: HDAC-1, -2, -4 and -6 protein expression was assessed immunohistochemically on 70 pancreatic adenocarcinoma tissue specimens and was statistically analyzed with clinicopathological characteristics and patients' survival. RESULTS: Enhanced HDAC-1 expression was significantly associated with increased tumor proliferative capacity (p = 0.0238) and borderline with the absence of lymph node metastases (p = 0.0632). Elevated HDAC-4 expression was significantly associated with the absence of organ metastases (p = 0.0453) and borderline with the absence of lymph node metastases (p = 0.0571) and tumor proliferative capacity (p = 0.0576). Enhanced HDAC-6 expression was significantly associated with earlier histopathological stage (p = 0.0115) and borderline with smaller tumor size (p = 0.0864). Pancreatic adenocarcinoma patients with enhanced HDAC-1 and -6 expression showed significantly longer survival times compared to those with low expression (p = 0.0022 and p = 0.0113, respectively), while a borderline association concerning HDAC-2 expression was noted (p = 0.0634). CONCLUSIONS: The present study suggested that HDACs may be implicated in pancreatic malignant disease progression, being considered of clinical utility with potential use as therapeutic targets.

Pregnane X Receptor Expression in Human Pancreatic Adenocarcinoma: Associations With Clinicopathologic Parameters, Tumor Proliferative Capacity, Patients' Survival, and Retinoid X Receptor Expression.

OBJECTIVES: Pregnane X receptor (PXR) has been involved in human malignancy, either by directly affecting carcinogenesis or by inducing drug-drug interactions and chemotherapy resistance. The present study aimed to assess the clinical significance of PXR in pancreatic adenocarcinoma. METHODS: Pregnane X receptor and its heterodimers' PXR/retinoid X receptor α (RXR-α), RXR-ß, and RXR-γ expression were assessed immunohistochemically on tumoral samples from 55 pancreatic adenocarcinoma patients and were associated with clinicopathologic parameters, tumor proliferative capacity, and patients' survival. RESULTS: Enhanced PXR expression was noted in 24 (43.6%) of 55 pancreatic adenocarcinoma cases. Pancreatic adenocarcinoma patients presenting increased histological grade of tumor differentiation showed a significant increased incidence of elevated PXR expression (P = 0.023). Enhanced PXR/RXR-ß expression was significantly associated with smaller tumor size and earlier clinical stage (P = 0.005 and P = 0.003, respectively). Elevated PXR/RXR-γ expression was significantly associated with smaller tumor size and earlier clinical stage (P = 0.012 and P = 0.014, respectively) and borderline with the absence of lymph node metastases (P = 0.056). In addition, pancreatic adenocarcinoma patients presenting enhanced PXR/RXR-γ expression showed marginally longer survival times compared with those with decreased expression (log-rank test, P = 0.053). CONCLUSIONS: This study supported evidence that PXR and its copartners' overexpression may be associated with favorable clinicopathologic parameters and better outcome in pancreatic adenocarcinoma.

Expression and promoter methylation status of hMLH1, MGMT, APC, and CDH1 genes in patients with colon adenocarcinoma.

Colorectal cancer (CRC) is the third most common cancer in men and the second in women worldwide. CRC development is the result of genetic and epigenetic alterations accumulation in the epithelial cells of colon mucosa. In the present study, DNA methylation, an epigenetic event, was evaluated in tumoral and matching normal epithelium in a cohort of 61 CRC patients. The results confirmed and expanded knowledge for the tumor suppressor genes hMLH1, MGMT, APC, and CDH1. Promoter methylation was observed for all the examined genes in different percentage. A total of 71% and 10% of the examined cases were found to be methylated in two or more and in all genes, respectively. mRNA and protein levels were also evaluated. Promoter methylation of hMLH1, MGMT, APC, and CDH1 genes was present at the early stages of tumor's formation and it could also be detected in the normal mucosa. Correlations of the methylated genes with patient's age and tumor's clinicopathological characteristics were also observed. Our findings suggest that DNA methylation is a useful marker for tumor progression monitoring and that promoter methylation in certain genes is associated with more advanced tumor stage, poor differentiation, and metastasis.

The role of serum total ghrelin level elevation in colon cancer patients.

PURPOSE: Many studies have pointed out a possible role of ghrelin, in the pathogenesis and natural history of gastrointestinal tract malignancies. The objective of this study was to estimate serum total ghrelin levels (STGL) in patients with colon cancer (CC) and to evaluate the value of this assay in research and clinical practice. METHODS: STGL were measured pre-operatively in 95 CC patients and in 39 healthy controls, and were correlated with patients' age, gender, body mass index (BMI), tumor location, Dukes stage, grade of differentiation and patients' survival. RESULTS: STGL were significantly elevated in patients with CC (127.6±34.5 pmol/L) vs healthy controls (89.3±19 pmol/L, p<0.05). STGL were significantly higher in endstage (180±10 pmol/L) vs initial-stage CC (94.2±22.6 pmol/L; p<0.05). Furthermore, patients with poorly differentiated tumors had statistically significantly higher STGL (144.5±30.7 pmol/L) compared to those with well (91.8±23.6 pmol/L) or moderately well (126±34 pmol/L) differentiated CC cases (p<0.05). No statistically significant differences in the patients' STGL were noticed with respect to their demographic/ clinical characteristics, tumor location and survival (p>0.05). CONCLUSIONS: The obtained results showed a link between elevated STGL and CC, suggesting that colon tumors contribute to ghrelin's production.

Invasive and ultrasound based monitoring of the intracranial pressure in an experimental model of epidural hematoma progressing towards brain tamponade on rabbits.

INTRODUCTION: An experimental epidural hematoma model was used to study the relation of ultrasound indices, namely, transcranial color-coded-Doppler (TCCD) derived pulsatility index (PI), optic nerve sheath diameter (ONSD), and pupil constriction velocity (V) which was derived from a consensual sonographic pupillary light reflex (PLR) test with invasive intracranial pressure (ICP) measurements. MATERIAL AND METHODS: Twenty rabbits participated in the study. An intraparenchymal ICP catheter and a 5F Swan-Ganz catheter (SG) for the hematoma reproduction were used. We successively introduced 0.1 mL increments of autologous blood into the SG until the Cushing reaction occurred. Synchronous ICP and ultrasound measurements were performed accordingly. RESULTS: A constant increase of PI and ONSD and a decrease of V values were observed with increased ICP values. The relationship between the ultrasound variables and ICP was exponential; thus curved prediction equations of ICP were used. PI, ONSD, and V were significantly correlated with ICP (r² = 0.84 ± 0.076, r² = 0.62 ± 0.119, and r² = 0.78 ± 0.09, resp. (all P < 0.001)). CONCLUSION: Although statistically significant prediction models of ICP were derived from ultrasound indices, the exponential relationship between the parameters underpins that results should be interpreted with caution and in the current experimental context.

Individual patient data systematic review and meta-analysis of optic nerve sheath diameter ultrasonography for detecting raised intracranial pressure: protocol of the ONSD research group.

BACKGROUND: The purpose of the optic nerve sheath diameter (ONSD) research group project is to establish an individual patient-level database from high quality studies of ONSD ultrasonography for the detection of raised intracranial pressure (ICP), and to perform a systematic review and an individual patient data meta-analysis (IPDMA), which will provide a cutoff value to help physicians making decisions and encourage further research. Previous meta-analyses were able to assess the diagnostic accuracy of ONSD ultrasonography in detecting raised ICP but failed to determine a precise cutoff value. Thus, the ONSD research group was founded to synthesize data from several recent studies on the subject and to provide evidence on the diagnostic accuracy of ONSD ultrasonography in detecting raised ICP. METHODS: This IPDMA will be conducted in different phases. First, we will systematically search for eligible studies. To be eligible, studies must have compared ONSD ultrasonography to invasive intracranial devices, the current reference standard for diagnosing raised ICP. Subsequently, we will assess the quality of studies included based on the QUADAS-2 tool, and then collect and validate individual patient data. The objectives of the primary analyses will be to assess the diagnostic accuracy of ONSD ultrasonography and to determine a precise cutoff value for detecting raised ICP. Secondly, we will construct a logistic regression model to assess whether patient and study characteristics influence diagnostic accuracy. DISCUSSION: We believe that this IPD MA will provide the most reliable basis for the assessment of diagnostic accuracy of ONSD ultrasonography for detecting raised ICP and to provide a cutoff value. We also hope that the creation of the ONSD research group will encourage further study. TRIAL REGISTRATION: PROSPERO registration number: CRD42012003072.

Optimization of Cannula Visibility during Ultrasound-Guided Subclavian Vein Catheterization, via a Longitudinal Approach, by Implementing Echogenic Technology.

Objective. One limitation of ultrasound-guided vascular access is the technical challenge of visualizing the cannula during insertion into the vessel. We hypothesized that the use of an echogenic vascular cannula (EC) would improve visualization when compared with a nonechogenic vascular cannula (NEC) during real-time ultrasound-guided subclavian vein (SCV) cannulation in the ICU. Material and Methods. Eighty mechanically ventilated patients were prospectively enrolled in a randomized study that was conducted in a medical-surgical ICU. Forty patients underwent EC and 40 patients were randomized to NEC. The procedure was ultrasound-guided SCV cannulation via the infraclavicular approach on the longitudinal axis. Results. The EC group exhibited increased cannula visibility as compared to the NEC group (92%±3% versus 85 ± 7%, resp., P < 0.01). There was strong agreement between the procedure operators and independent observers (k = 0.9, 95% confidence intervals assessed by bootstrap analysis = 0.87 to 0.93; P < 0.01). Access time (12.1 s ± 6.5 versus 18.9 s ± 10.9) and the perceived technical difficulty of the ultrasound method (4.5 ± 1.5 versus 7.5 ± 1.5) were both decreased in the EC group compared to the NEC group (P < 0.05). Conclusions. Echogenic technology significantly improved cannula visibility and decreased access time and technical complexity optimizing thus real-time ultrasound-guided SCV cannulation via a longitudinal approach.

Correlation of Peroxisome Proliferator-Activated Receptor-gamma (PPAR-gamma) and Retinoid X Receptor-alpha (RXR-alpha) expression with clinical risk factors in patients with advanced carotid atherosclerosis.

BACKGROUND: Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) and its nuclear partners, the Retinoid X Receptors (RXRs), have been recognized as crucial players in the pathogenesis of atherosclerosis. The present study aimed to assess the clinical significance of PPAR-gamma and RXR-alpha expression in different cellular populations localized within advanced carotid atherosclerosis lesions. MATERIAL/METHODS: PPAR-gamma and RXR-alpha expression was assessed by immunohistochemistry in 134 carotid atherosclerotic plaques obtained from an equal number of patients that underwent endarterectomy procedure for vascular repair, and was correlated with patients' medical history, risk factors and medication intake. RESULTS: Increased incidence of low PPAR-gamma expression in both macrophages and smooth muscle cells was noted in patients presenting coronary artery disease (p=0.032 and p=0.046, respectively). PPAR-gamma expression in smooth muscle cells was borderline down-regulated in symptomatic compared to asymptomatic patients (p=0.061), reaching statistical significance when analyzing groups of patients with specific cerebrovascular events; amaurosis fugax (p=0.008), amaurosis fugax/stroke (p=0.020) or amaurosis fugax/transient ischemic attack patients (p=0.028) compared to asymptomatic patients. Low RXR-alpha expression in macrophages was more frequently observed in hypertensive (p=0.048) and hyperlipidemic patients (p=0.049). Increased incidence of low RXR-alpha expression in smooth muscle cells was also noted in patients presenting advanced carotid stenosis grade (p=0.015). CONCLUSIONS: PPAR-gamma and RXR-alpha expression down-regulation in macrophages and smooth muscle cells was associated with a more pronounced disease progression in patients with advanced carotid atherosclerotic lesions.

Real-time ultrasound-guided subclavian vein cannulation versus the landmark method in critical care patients: a prospective randomized study.

OBJECTIVE: Subclavian vein catheterization may cause various complications. We compared the real-time ultrasound-guided subclavian vein cannulation vs. the landmark method in critical care patients. DESIGN: Prospective randomized study. SETTING: Medical intensive care unit of a tertiary medical center. PATIENTS: Four hundred sixty-three mechanically ventilated patients enrolled in a randomized controlled ISRCTN-registered trial (ISRCTN-61258470). INTERVENTIONS: We compared the ultrasound-guided subclavian vein cannulation (200 patients) vs. the landmark method (201 patients) using an infraclavicular needle insertion point in all cases. Catheterization was performed under nonemergency conditions in the intensive care unit. Randomization was performed by means of a computer-generated random-numbers table and patients were stratified with regard to age, gender, and body mass index. MEASUREMENTS AND MAIN RESULTS: No significant differences in the presence of risk factors for difficult cannulation between the two groups of patients were recorded. Subclavian vein cannulation was achieved in 100% of patients in the ultrasound group as compared with 87.5% in the landmark one (p < .05). Average access time and number of attempts were significantly reduced in the ultrasound group of patients compared with the landmark group (p < .05). In the landmark group, artery puncture and hematoma occurred in 5.4% of patients, respectively, hemothorax in 4.4%, pneumothorax in 4.9%, brachial plexus injury in 2.9%, phrenic nerve injury in 1.5%, and cardiac tamponade in 0.5%, which were all increased compared with the ultrasound group (p < .05). Catheter misplacements did not differ between groups. In this study, the real-time ultrasound method was rated on a semiquantitative scale as technically difficult by the participating physicians. CONCLUSIONS: The present data suggested that ultrasound-guided cannulation of the subclavian vein in critical care patients is superior to the landmark method and should be the method of choice in these patients.

MCM-2 and MCM-5 expression in gastric adenocarcinoma: clinical significance and comparison with Ki-67 proliferative marker.

BACKGROUND: Minichromosome maintenance (MCM) proteins are essential components of DNA replication, being related to cell proliferation, and serve as useful biomarkers for cancer screening, surveillance and prognosis. The aim of the present study was to evaluate the clinical significance of MCM-2 and MCM-5 expression in gastric adenocarcinoma in comparison with Ki-67 proliferative marker. METHODS: MCM-2, MCM-5 and Ki-67 expression was assessed immunohistochemically in 66 tumoral samples of gastric adenocarcinoma patients and was statistically analyzed in relation to clinicopathological characteristics and patient survival. RESULTS: MCM-2 expression did not show significant associations with any clinicopathological parameters, while Ki-67 expression was merely significantly associated with tumor size (P = 0.0150). MCM-2 and Ki-67 expression were more frequently in intestinal (median values: 67.5 and 60%) compared to diffuse-type (median values: 60 and 45%) gastric adenocarcinoma cases without though reaching statistical significance (P > 0.05). MCM-5 expression was significantly associated with tumor size (P = 0.0295), presence of lymph node metastases (P = 0.0216) and tumor histopathological stage (P = 0.0098). Patients presenting high MCM-5 expression had significantly shorter survival times (log-rank test, P = 0.0042), whereas neither MCM-2 nor Ki-67 expression showed significant prognostic value (log-rank test, P = 0.9618 and P = 0.7174, respectively). In multivariate analysis, patient age, histopathological stage and grade of differentiation, but not MCM-5 expression, were identified as independent prognostic factors (Cox regression analysis, P = 0.0097, P = 0.0195, P = 0.0035 and P = 0.3245, respectively). CONCLUSIONS: The present study showed that MCM-5 expression was associated with clinicopathological parameters in gastric adenocarcinoma. However, further studies highlighting the distinct impact of the two histopathological types, intestinal and diffuse, are warranted to delineate whether MCMs could be used as diagnostic and prognostic markers in gastric neoplasia.

Platelet-activating factor involvement in thioacetamide-induced experimental liver fibrosis and cirrhosis.

Platelet-activating factor (PAF) is a potent lipid inflammatory mediator acting on cells through its specific receptor. Plasma PAF-acetylhydrolase (PAF-AH) is the main enzyme that inactivates PAF in blood, participating in its homeostasis. The objective of this study was to investigate the involvement of PAF in the liver fibrotic process using an experimental animal model. Liver fibrosis was induced in adult male Wistar rats by administration of thioacetamide (TAA) in drinking water (300 mg/l) for three months. The animals were sacrificed at time 0 (control group) and after 1, 2, and 3 months. PAF levels in liver and blood and PAF-AH activity in plasma were determined. Liver histopathological examination was also performed. TAA administration resulted in progressively increased liver fibrosis, leading finally to the formation of cirrhotic nodules in the liver. Throughout the experiment PAF levels in liver tissue remained stable. "Total" ("free" plus "bound") PAF levels in blood decreased, reaching statistically significant differences in the first and third months compared with the control group (P < 0.05). "Free" PAF levels in blood were higher at one month (P < 0.05) and decreased gradually thereafter. In all treated groups, "bound" PAF levels in blood decreased whereas plasma PAF-AH activity increased (P < 0.05) compared with the control group. Our data indicated alterations of PAF levels in blood and PAF-AH activity during fibrosis induction, implicating participation of PAF in the liver fibrotic process.

Clinical significance of ephrin (eph)-A1, -A2, -a4, -a5 and -a7 receptors in pancreatic ductal adenocarcinoma.

Ephrin (Eph) receptors have been reported to be frequently overexpressed in a wide variety of cancer types, being associated with tumor growth, invasion, metastasis and angiogenesis. The aim of the present study was to evaluate the clinical significance of Eph-A1, -A2, -A4, -A5 and -A7 expression in pancreatic ductal adenocarcinoma. Eph-A1, -A2, -A4, -A5 and -A7 expression and staining intensity were assessed immunohistochemically in tumoral samples of 67 pancreatic adenocarcinoma patients and were statistically analyzed in relation to clinicopathological characteristics, tumor proliferative capacity and patients' survival. Eph receptors were abundantly expressed in pancreatic ductal adenocarcinoma cases examined. Eph-A1 staining intensity was significantly associated with tumor size (pT, p = 0.008) and tumor histopathological stage (pStage, p = 0.012). Eph-A2 expression was significantly associated with patients' age (p = 0.007), while Eph-A4 and Eph-A5 with tumor proliferative capacity (p = 0.019 and p = 0.011, respectively). Pancreatic adenocarcinoma patients with moderate/intense Eph-A5 or Eph-A7 staining presented significantly shorter survival times compared to those with negative/mild one (log-rank test, p = 0.024 and p = 0.009, respectively). Multivariate analysis identified Eph-A5 and Eph-A7 staining intensity as independent prognostic factors (p = 0.048 and p = 0.004, respectively). In conclusion, the present study revealed that Eph receptors were associated with pancreatic cancer characteristics, supporting evidence for their potential clinical application in management and prognosis of pancreatic adenocarcinoma patients.

Peroxisome proliferator-activated receptor-gamma and retinoid X receptor-alpha expression in pancreatic ductal adenocarcinoma: association with clinicopathological parameters, tumor proliferative capacity, and patients' survival.

BACKGROUND: Peroxisome proliferator-activated receptor-gamma (PPAR-gamma), a ligand-activated transcription factor that forms heterodimers with the retinoid X receptors (RXRs), is overexpressed in various tumors, regulating many aspects of cancer biology. The aim of the present study was to evaluate the clinical significance of PPAR-gamma and RXR-alpha expression in pancreatic adenocarcinoma. MATERIAL/METHODS: PPAR-gamma and RXR-alpha protein expression was assessed immunohistochemically in tumoral samples of 65 pancreatic adenocarcinoma patients and statistically analyzed in relation to clinicopathological characteristics, tumor proliferative capacity, and patients' survival. RESULTS: Of the 65 adenocarcinoma patients, 49 (75%) tested positive for PPAR-gamma and 55 (85%) stained positive for RXR-alpha. RXR-alpha positivity was significantly associated with tumor proliferative capacity and PPAR-gamma positivity (p=0.022 and p=0.043, respectively). PPAR-gamma and RXR-alpha staining intensity were associated with the histopathological tumor grade (p=0.003 and p=0.038, respectively). Significant associations of PPAR-gamma staining intensity and RXR-alpha expression with tumor size were also noted (p=0.041 and p=0.038, respectively). Moderate and intense PPAR-gamma staining intensity was associated with shorter overall survival in univariate analysis (log-rank test, p=0.023) and proved to be an independent prognostic factor in multivariate analysis (p=0.045), whereas RXR-alpha failed to predict patients' survival. CONCLUSIONS: These data revealed that both PPAR-gamma and RXR-alpha were associated with pancreatic cancer characteristics. PPAR-gamma, but not RXR-alpha, was found to be an independent prognostic indicator. However, further molecular and clinical studies are required to delineate the potential clinical application of PPAR-gamma and RXR-alpha in the prognosis and management of pancreatic adenocarcinoma patients.

Heat Shock Protein-27, -60 and -90 expression in gastric cancer: association with clinicopathological variables and patient survival.

BACKGROUND: Heat shock proteins (HSPs) are ubiquitous, highly conserved proteins across all the species and play essential roles in maintaining protein stability within the cells under normal conditions, while preventing stress-induced cellular damage. HSPs were also overexpressed in various types of cancer, being associated with tumor cell proliferation, differentiation and apoptosis. The aim of the present study was to evaluate the clinical significance of HSP -27, -60, and -90 expression in gastric carcinoma. METHODS: HSP -27, -60, and -90 proteins expression was assessed immunohistochemically in tumoral samples of 66 gastric adenocarcinoma patients and was statistically analyzed in relation to various clinicopathological characteristics, tumor proliferative capacity and patients' survival. RESULTS: HSP-27, -60, -90 proteins were abundantly expressed in gastric adenocarcinoma cases examined. HSP-27 expression was significantly associated with tumor size (pT, P = 0.026), the presence of organ metastases (pM, P = 0.046) and pStage (P = 0.041), while HSP-27 staining intensity with nodal status (pN, P = 0.042). HSP-60 expression was significantly associated with patients' sex (P = 0.011), while HSP-60 staining intensity with patients' age (P = 0.027) and tumor histopathological grade (P = 0.031). HSP-90 expression was not associated with any of the clinicopathological parameters examined; however, HSP-90 staining intensity was significantly associated with tumor size (pT, P = 0.020). High HSP-90 expression was significantly associated with longer overall survival times in univariate analysis (log-rank test, P = 0.033), being also identified as an independent prognostic factor in multivariate analysis (P = 0.026). CONCLUSION: HSP-27, -60, and -90 were associated with certain clinicopathological parameters which are crucial for the management of gastric adenocarcinoma patient. HSP-90 expression may also be an independent prognostic indicator in gastric adenocarcinoma patients.

Expression and clinical significance of focal adhesion kinase in the two distinct histological types, intestinal and diffuse, of human gastric adenocarcinoma.

Focal adhesion kinase (FAK), a non-receptor tyrosine kinase protein, acts as an early modulator of integrin signaling cascade, regulating basic cellular functions. In transformed cells, unopposed FAK signaling has been considered to promote tumor growth, progression and metastasis. The aim of this study was to assess the clinical significance of FAK expression in the two distinct histological types of human gastric neoplasia. FAK expression was assessed immunohistochemically in tumoral samples of 66 gastric adenocarcinoma cases, 30 intestinal and 36 diffuse type, and was statistically analyzed in relation to various clinicopathological characteristics, tumor proliferative capacity and patients' survival. In intestinal type carcinomas, enhanced FAK expression was significantly associated with increased tumor proliferative capacity (P = 0.012). In diffuse type carcinomas, FAK staining intensity was significantly correlated with tumor size (P = 0.026) and disease stage (P = 0.024), presenting also a borderline association with nodal status (P = 0.053). In diffuse type carcinomas, enhanced FAK expression was significantly associated with longer overall survival times (log-rank test, P = 0.014), being also identified as an independent prognostic factor in multivariate analysis (Cox regression, P = 0.016). In contrast, patients with intestinal type tumors and enhanced FAK expression were characterized by shorter overall survival times, without though reaching statistical significance (log-rank test, P = 0.092). The current data support evidence that FAK protein may be considered as a diagnostic and prognostic marker in gastric neoplasia. Further studies conducted on larger clinical samples and highlighting on the distinct impact of the two histological types are warranted to delineate the clinical significance of FAK protein in gastric neoplasia.

Clinical significance of MCM-2 and MCM-5 expression in colon cancer: association with clinicopathological parameters and tumor proliferative capacity.

Minichromosome maintenance (MCM) proteins are essential components of DNA replication, being related to cell proliferation, and serve as useful markers for cancer screening, surveillance, and prognosis. Our aim was to examine the clinical significance of MCM-2 and MCM-5 protein expression in colon cancer and to evaluate the association with various clinicopathological characteristics and tumor proliferative capacity. Immunohistochemical expression of MCM-2 and MCM-5 was performed on paraffin-embedded malignant tissue sections obtained from 96 patients with colon cancer. MCM-2 and MCM-5 expression was correlated with different clinicopathological characteristics, proliferative capacity (Ki-67 labeling index), and p53 cell-cycle regulator expression. MCM-2 and Ki-67 expression was significantly associated with the tumors' histological grade (P = 0.003), existence of nodular metastases (N) (P = 0.003 and P = 0.030, respectively), malignancy on adenoma (P = 0.029 and P = 0.024, respectively), and vascular invasion (P = 0.010 and P = 0.011, respectively). MCM-2 expression was additionally associated with Dukes' stage (P = 0.005). Significant positive relationships were found between the expression of MCM-2 or MCM-5 proteins and that of Ki-67 protein (r = 0.963, P-value < 0.001, and r = 0.738, P-value < 0.001, respectively), as well as between MCM-2 and MCM-5 proteins (r = 0.745, P-value < 0.001). Significant positive relationships were also observed between the expression of MCM-2 or MCM-5 proteins and that of p53 protein; however, they were consistently lower than the corresponding with Ki-67 protein. No significant association was observed between MCM-5 protein expression and the clinicopathological characteristics examined. The current data suggest that MCM-2 protein expression is significantly associated with important clinicopathological characteristics for patients' management, being correlated with the cell proliferation state in colon cancer.