Tumor Histological Differentiation Research Articles

Altered expression of lysosomal associated membrane protein 1 in esophageal squamous cell carcinoma

BackgroundEsophageal squamous cell carcinoma (ESCC) is one of the most common cancers. LAMP1, major protein components of lysosome, is primarily located on the lysosomal membrane and rarely expressed on the surface of normal cells, playing an important role in the lysosome-mediated physiological processes. Previous studies confirmed that LAMP1 showed high expression in astrocytoma. The purpose of this study was to investigate the expression levels of LAMP1 and to discuss its roles in ESCC. MethodsWe collected 610 tissue samples of ESCC patients to construct tissue microarrays, which were subsequently stained by immunohistochemistry with LAMP1 antibody. ResultsAfter immunohistochemical staining, a total of 584 patients, including 453 men and 131 women, were analysed. The positive immunostaining was mainly located at the cytoplasm. The LAMP1 expression levels were significantly different between different T status (P<0.001), TNM stages (P<0.01) and degrees of tumor histological differentiation (P<0.001). Besides, LAMP1 expression levels were positively correlated with TNM stages (P<0.05). The higher the TNM stages, the higher the LAMP1 expression levels. Similar results also appeared in degrees of tumor histological differentiation (P<0.01), but not in ages, genders, tumor size, T status, lymphatic metastasis and tumor locations (P>0.05). ConclusionLAMP1 is involved in the TNM stages and histological differentiation of the ESCC. Targeted therapy for LAMP1 may be a promising novel therapeutic strategy against poorly differentiated ESCC.

CYFIP1 is directly controlled by NOTCH1 and down-regulated in cutaneous squamous cell carcinoma.

Squamous cell carcinoma of the skin (SCC) represents one of the most common cancers in the general population and is associated with a substantial risk of metastasis. Previous work uncovered the functional role of CYFIP1 in epithelial tumors as an invasion inhibitor. It was down-regulated in some cancers and correlated with the metastatic properties of these malignant cells. We investigated its role and expression mechanisms in SCC. We analyzed the expression of CYFIP1 in patient derived SCC, primary keratinocytes and SCC cell lines, and correlated it to the differentiation and NOTCH1 levels. We analyzed the effects of Notch1 manipulation on CYFIP1 expression and confirmed the biding of Notch1 to the CYFIP1 promoter. CYFIP1 expression was down-regulated in SCC and correlated inversely with histological differentiation of tumors. As keratinocyte differentiation depends on Notch1 signaling, we investigated the influence of Notch1 on CYFIP1 expression. CYFIP1 mRNA was highly increased in human Notch1-overexpressing keratinocytes. Further manipulation of the Notch1 pathway in keratinocytes impacted CYFIP1 levels and chromatin immunoprecipitation assay confirmed the direct binding of Notch1 to the CYFIP1 promoter. CYFIP1 may be a link between loss of differentiation and invasive potential in malignant keratinocytes of cutaneous squamous cell carcinoma.

Expression of E-Cadherin/Beta-Catenin in Epithelial Carcinomas of the Thyroid Gland.

BACKGROUND:The aberrant activation of Wnt signalling pathway may be a common denominator for the development of thyroid tumorigenesis. It was announced that the loss of E-cadherin rather than β-catenin mutation represents a crucial event in determining the degree of differentiation of thyroid carcinomas.AIM:The aim of the study was to evaluate the expression of E-cadherin and β-catenin in the thyroid cancer tissue and to correlate these data with some histological and clinical parameters of the tumours.MATERIAL AND METHODS:We investigated 112 patients, having thyroid tumours – papillary, follicular, anaplastic and oncocytic carcinomas immunohistochemically with antibodies against E-cadherin and β-catenin. Survival analyses were done.RESULTS:E-cadherin expression was focally retained in the tumour cell membranes and the tumour cell cytoplasm of the papillary, follicular and oncocytic thyroid cancers, weather in anaplastic cancers it was almost lost (p = 0.0042, and p = 0.019, respectively, Fisher’s Exact Test). The expression of β-catenin in tumour cytoplasm and membrane in papillary cancers was higher as compared to that in the other tumours (p = 0.111, and p = 0.0104, respectively).CONCLUSION:Not surprisingly, the presence of aberrant expression of E-cadherin and β-catenin in thyroid cancer has been associated with better patients’ prognosis and better differentiated tumour histology.

Prospective evaluation of the clinical implications of the tumor metabolism and chemotherapy-related changes in advanced biliary tract cancer.

261 Background: Tumor metabolism measured by [18F] fluorodeoxy-D-glucose (18F-FDG) positron emission tomography (PET) has a diagnostic and prognostic role in several cancers. The clinical implication of tumor metabolism in biliary tract cancer (BTC) has not been studied well. Therefore, we prospectively evaluated the prognostic value of tumor metabolism and chemotherapy-related changes in advanced BTC patients. Methods: We prospectively enrolled advanced BTC patients before the initiation of palliative chemotherapy. Using 18F-FDG PET, we assessed the baseline maximum standardized uptake value (SUVmax) and monitored the changes of SUVmax during chemotherapy. We analyzed the associations between SUVmax, and clinicopathologic factors and clinical outcomes. Results: A total of 75 patients were enrolled. All patients received gemcitabine/cisplatin as first-line chemotherapy. Primary tumor site, histologic differentiation, molecular characteristics, laboratory findings, and disease extent were associated with the metabolic characteristics. The high metabolism group showed worse survival outcome [Hazard ratio (HR)=4.09, p=0.001 for progression-free survival (PFS); HR=2.61, p=0.019 for overall survival (OS)] than the low metabolism group. The lesser reduction of SUVmax during chemotherapy was also associated with worse outcome (HR=3.35, p=0.002 for PFS; HR=1.96, p=0.082 for OS). Considering both baseline tumor metabolic activity and chemotherapy-related changes in the tumor metabolism, patients with a low metabolism and a more reduction in metabolism obtained the best OS (20.7 months, p=0.013). Conclusions: Tumor metabolic activity and the chemotherapy-related changes in the metabolism were associated with prognosis in advanced BTC patients.

Correlation of Positron Emission Tomography/Computed Tomography Scan with Smoking, Tumor Size, Stage and Differentiation in Head and Neck Cancer Patients.

The goal of this study was to identify associations between positron emission tomography/computed tomography (PET/CT) maximum standardized uptake value (SUVmax) in patients presenting with head and neck squamous cell carcinoma (SCC) with tumor site, size, histologic differentiation, smoking, and diabetes. Charts of patients with oropharyngeal and laryngeal SCC who underwent 18F-fluorodeoxyglucose PET/CT scans were reviewed between May 2007 and August 2013. Statistical analyses included modeling log-transformed SUVmax values by tumor site, size, histologic differentiation, smoking status, and diabetes using unadjusted linear regressions. Differences were considered statistically significant for P< 0.05. A total of 111 patients (54 with oropharynx and 57 with larynx cancers) were included, 83 men and 28 women with an average age of 57.5 years old. There was a significantly higher pack-year smoking history (P = 0.005) in the larynx cancer group. While tumor T-stage was found to be significantly different (P < 0.0001), there was no difference in tumor size between the two groups: 3.16 cm and 3.58 cm in the oropharynx and larynx, respectively (P = 0.55). In the oropharynx cohort, SUVmax was associated with both tumor size (P = 0.0001) and stage (P < 0.0002). Interestingly, SUVmax differed by tumor differentiation in the larynx (P = 0.04) but not the oropharynx (P = 0.71). Finally, there was no significant difference in SUVmax relative to diabetes and smoking status. PET/CT SUVmax correlated with both tumor size and stage in oropharyngeal cancer patients, and it correlated only with tumor differentiation but not the size or stage in the larynx. There were no significant differences in SUVmax by diabetes or smoking status.

Can lymphovascular invasion be predicted by preoperative multiphasic dynamic CT in patients with advanced gastric cancer?

To determine whether multiphasic dynamic CT can preoperatively predict lymphovascular invasion (LVI) in advanced gastric cancer (AGC). 278 patients with AGC who underwent preoperative multiphasic dynamic CT were retrospectively recruited. Tumour CT attenuation difference between non-contrast and arterial (ΔAP), portal (ΔPP) and delayed phase (ΔDP), tumour-spleen attenuation difference in the portal phase (ΔT-S), tumour contrast enhancement ratios (CERs), tumour-to-spleen ratio (TSR) and tumour volumes were obtained. All CT-derived parameters and clinicopathological variables associated with LVI were analysed by univariate analysis, followed by multivariate and receiver operator characteristics (ROC) analysis. Associations between CT predictors for LVI and histopathological characteristics were evaluated by the chi-square test. ΔPP (OR, 1.056; 95% CI: 1.032-1.080) and ΔT-S (OR, 1.043; 95% CI: 1.020-1.066) are independent predictors for LVI in AGC. ΔPP, ΔT-S and their combination correctly predicted LVI in 74.8% (AUC, 0.775; sensitivity, 88.6%; specificity, 54.1%), 68.7% (AUC, 0.747; sensitivity, 68.3%; specificity, 69.4%) and 71.7% (AUC, 0.800; sensitivity, 67.6%; specificity, 77.8%), respectively. There were significant associations between CT predictors for LVI with tumour histological differentiation and Lauren classification. Multiphasic dynamic CT provides a non-invasive method to predict LVI in AGC through quantitative enhancement measurement. • Lymphovascular invasion rarely can be evaluated preoperatively in advanced gastric cancer (AGC). • Δ PP and Δ T-S were independent predictors for LVI in patients with AGC. • Δ PP and Δ T-S showed acceptable predictive performance for LVI. • Combination of Δ PP and Δ T-S improved predictive performance for LVI. • Multiphasic dynamic CT may be a useful adjunct for detecting LVI preoperatively.

Overexpression of PD-L1 and PD-L2 Is Associated with Poor Prognosis in Patients with Hepatocellular Carcinoma.

PurposeHepatocellular carcinoma (HCC) is one of the most aggressive malignancies. Recently, the overexpression of programmed cell death 1 (PD-1) and PD-1 ligand 1 (PD-L1) has been shown to correlate with poor prognosis in many cancers. However, the expression of PD-L1 or PD-1 ligand 2 (PD-L2) and clinical outcomes have not been fully investigated in HCC.Materials and MethodsFormalin-fixed paraffin-embedded samples were obtained from 85 patients with HCC who underwent surgery. The expression of PD-Ls (PD-L1, PD-L2) was evaluated by immunohistochemical analysis.ResultsThe proportion of high expression groups of PD-L1 and PD-L2 was 27.1% and 23.5%, respectively. Univariate analysis revealed that tumor size (p < 0.001), histological differentiation (p=0.010), PD-L1 expression (p < 0.001), and PD-L2 expression (p=0.039) were significant prognostic factors of overall survival in patients with HCC. Multivariate analysis revealed that overall tumor size (hazard ratio [HR], 4.131; 95% confidence interval [CI], 2.233 to 7.643; p < 0.001 and HR, 3.455; 95% CI, 1.967 to 6.067; p < 0.001) and PD-L1 expression (HR, 5.172; 95% CI, 2.661 to 10.054; p < 0.001 and HR, 3.730; 95% CI, 1.453 to 9.574; p=0.006) were independent prognostic values for overall and disease-free survival. Patients with high expression of PD-Ls had a significantly poorer survival than those with low expression (p < 0.001, p=0.034).ConclusionThe overexpression of PD-Ls in HCC patients is correlated with survival and tumor recurrence. Further evaluation of PD-1 and PD-Ls as therapeutic targets and predictive biomarkers for HCC is warranted.

The prognostic role and reduced expression of FOXJ2 in human hepatocellular carcinoma.

The current study aimed to investigate the potential role of the FOXJ2 (forkhead box J2) protein in the pathology of hepatocellular carcinoma (HCC). Western blotting was performed to determine the expression levels of FOXJ2 in HCC tissues and HCC cells. Specimens from 110 patients with HCC undergoing hepatic resection were evaluated for FOXJ2 expression using an immunohistochemical assay. The correlation between FOXJ2 expression and clinicopathological factors of the patients was determined by statistical analysis to determine the prognostic merit of FOXJ2 expression in HCC. The detailed involvement of FOXJ2 in the regulation of HCC proliferation was further investigated using FOXJ2-targeting small interfering RNA (siRNA). FOXJ2 protein was identified to be significantly downregulated in HCC tissues compared with adjacent normal liver tissues. Immunohistochemical analysis demonstrated that the expression of FOXJ2 was negatively correlated with Ki-67 levels in HCC specimens (r=−0.679, P<0.001). Furthermore, statistical analysis indicated FOXJ2 expression was significantly associated with histological differentiation (P=0.005), the size of largest tumor (P=0.002) and metastasis (P=0.036). Using Kaplan-Meier analysis, it was demonstrated that high FOXJ2 expression levels predicted significantly improved patient survival rates compared with low FOXJ2 expression levels (P<0.001). In addition, it was observed that interference of FOXJ2 expression using siRNA oligos led to the promotion of proliferation of HepG2 cells. FOXJ2 was markedly downregulated in HCC tissues. The expression of FOXJ2 was correlated with tumor size, histological differentiation and metastasis. Low expression levels of FOXJ2 predicted poor prognosis for patients with HCC, suggesting that FOXJ2 may be a candidate prognostic marker of HCC. Depletion of FOXJ2 caused the promotion of HCC cell proliferation, implicating that FOXJ2 may serve an inhibitory role in the regulation of HCC cell proliferation.

Preoperative cognitive function predicts survival in patients with resectable pancreatic ductal adenocarcinoma

Aims: Staging and prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) are defined by tumor stages according to the AJCC Cancer Staging Manual (TNM staging system). Multiple previous studies have demonstrated that clinicopathological factors such as tumor size, histologic differentiation, margin status, and nodal involvement are statistically significant prognostic variables for survival in patients undergoing resection for pancreatic cancer. The purpose of this study was to evaluate whether pre-surgery health-related quality of life (HRQoL) and subjectively rated symptom scores are independent prognostic factors for survival in patients with resectable PDAC. Methods: A prospective study of patients undergoing pancreatic resection for PDAC was conducted from November 2008 to December 2011. Patients completed the Edmonton Symptom Assessment System (ESAS) and the European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-PAN26 questionnaires prior to surgery. Patient, tumor and treatment characteristics, and recurrence and survival were registered. Results: A total of 66 consecutive patients (male n=30/female n=36, median age 68 years) underwent R0/R1 resection for PDAC. Baseline ESAS and EORTC questionnaire compliance was 44/66 (66.7%). There were no statistically significant difference between compliers (n=44) and non-compliers (n=22) when comparing clinicopathological parameters and survival. The univariate analyses showed that three symptoms (nausea, dry mouth and cognitive function) and two clinicopathological factors (CA 19–9 >400 U/ml, lymph node ratio >0.1) were significantly associated with shorter survival. In the multivariate analysis, cognitive function was the only independent predictor for survival. Patients with low (<66.67%) and high (≥66.67%) cognitive function had a median survival of 11 and 21 months (p<0.001), respectively. Conclusions: In the present sample, presurgery cognitive function was a significant independent predictor of survival in patients with resectable PDAC. Thus, presurgery HRQoL scores may provide as strong prognostic information as clinicopathological factors in patients with resectable PDAC and should be routinely assessed.

Tumeurs neuroendocrines digestives

Digestive neuroendocrine tumors (NETs) are a group of rare tumors with increasing incidence. Pathological analysis is critical to establish the diagnosis and evaluate tumor grade that relies on differentiation and proliferation index. NETs are mostly diagnosed at an advanced stage because of late occurrence of nonspecific symptoms, and can be associated with hormone hypersecretion. Chromogranin A is the main biochemical marker of NETs. Extension workup relies on conventional imaging (CT-scan, MRI) and isotopic imaging including somatostatin-receptor scintigraphy, which should be soon replaced by positron-emitting scintigraphy. The main prognostic factors include tumor stage, metastatic volume, histological differentiation and grade. Hormonal syndromes and poorly differentiated tumors are the two therapeutic emergencies. The treatment of localized well-differentiated tumors relies on endoscopic or surgical resection depending on the location and aggressiveness. Surgical removal is the only potentially curative treatment of metastatic NETs but is rarely feasible and is associated with almost constant relapse. Other antitumor therapies include somatostatin analogs, systemic chemotherapy, liver trans-arterial chemo-embolization, targeted therapies and peptide-receptor radionuclide therapy. Management strategy relies on primary tumor location, tumor aggressiveness, metastatic volume and the presence of extra-hepatic metastases. It must take into account the risk of cumulated toxicity in patients whose survival is often prolonged.

Patterns of recurrence in patients with stage pT3N0M0 thoracic esophageal squamous cell carcinoma after two-field esophagectomy

To evaluate the patterns of recurrence and the related factors in patients with pT3N0M0 thoracic esophageal squamous cell carcinoma (ESCC) after two-field esophagectomy. From Jan 2008 to Dec 2009, 208 patients with stage pT3N0M0(2002, UICC) thoracic ESCC were treated with two-field esophagectomy in our hospital. There were 138 males and 70 females, and the median age was 60 years old (range 33-78). There were 33 patients in the upper-, 134 in the middle-, and 41 in the lower-thoracic esophagus, with a median length of lesion of 5 cm. There were 32 patients with no-, 78 with mild- and 98 patients with severe adhesions at surgery. The median number of dissected lymph nodes was 9 (range 1-27). 98 patients were treated with surgery alone and 110 with postoperative adjuvant chemotherapy. The statistical analysis was conducted using SPSS 13.0 software. The follow-up was ended on July 2013. In the total group of 208 patients, the total recurrence rate was 41.8% (87/208). Among them, 52 patients had locoregional recurrence (LR), 15 had distant metastasis (DM) and 20 patients had both local recurrence and distant metastasis. 40.2% (35/87) of all recurrences were found within one year after operation, 67.8% (59/87) within 2 years, 86.2% (75/87) within 3 years, and 100% (87/87) within 4 years. The 1-, 3-, and 5-year progression-free survival (PFS) rate was 83.0%, 62.8% and 56.3%, respectively. The overall locoregional recurrence rate was 34.6% (72/208), among them, 9 cases had recurrence in the cervix (all were supraclavicular lymph node metastasis), 66 cases in the mediastinum and 4 cases had para-aortic lymph node metastasis. 83.3% (60/72) of the locoregional recurrence was located in the carinal region or upper area. The 1-, 3-, 5-year locoregional recurrence rate was 15.6%, 32.2%, and 36.8%, respectively, and the median time of recurrence was 15.5 months. The overall distant metastasis (DM) rate was 16.8% (35/208). The 1-, 3-, and 5-year DM rate was 4.4%, 15.3%, and 20.1%, respectively, and the median time of DM was 24 months. The most common site of DM was the lung and bone. The univariate analysis showed that age and tumor site were associated with PFS, tumor site and small lymph node in the mediastinum (diamter <1 cm) before surgery were related with LR (P<0.05 for all), and tumor site, histological differentiation and LR were related with distant metastasis after surgery (P<0.05). Multivariate analysis showed that the tumor site was an independent prognostic factor affecting the progression-free survival and locoregional recurrence (P<0.05), and histological differentiation and LR were independent factors associated with distant metastasis (P<0.05 for all). The recurrence rate is very high in patients with pT3N0M0 thoracic ESCC after surgery, and most of them occur within 3 years after operation. Locoregional recurrence occurs more frequently and shortly than distant metastasis, and most of LR is located in the carinal region or upper-mediastinum. LR rate in upper-thoracic ESCC is very high, therefore, postoperative radiotherapy (PORT) is strongly suggested. LR rate in middle thoracic ESCC is also rather high and PORT is suggested. LR occur much less in the lower-thoracic ESCC, thus, PORT is not suggested routinely. Patients with poorly differentiated ESCC and LR have a high rate of distant metastasis.

Analysis of the invasive edge in primary and secondary oral squamous cell carcinoma: An independent prognostic marker: A retrospective study

Background and Objectives:Oral squamous cell carcinoma (OSCC) is one of the most common head and neck carcinomas and corresponds to 95% of all oral cancers with an increasing morbidity and mortality. Its prognosis is affected by several clinicopathologic factors, one of which is pattern of invasion (POI). The histological features of OSCC may differ widely, but there is general agreement that the most useful prognostic information can be deduced from the invasive front of the tumor. In this retrospective study, our aim was to compare the POI, the status of connective tissue and the status of inflammation at the tumor–host interface in primary and recurrent (secondary) OSCC and test the validity of POI, to serve as a potential marker to assess the prognosis of the patient.Materials and Methods:Differentiation of tumors, POI, status of connective tissue and inflammation was assessed in 168 cases of primary and recurrent cases of OSCC.Statistical Analysis:Fisher's exact test was used to determine the statistical significance and P < 0.05 was considered to be statistically significant.Results:Our study showed that majority of the primary and secondary tumors were well differentiated, 117 [95.9%] and 34 [73.9%], respectively. Predominant POI in the primary and secondary tumor group was Pattern II and least was Pattern V. Worst pattern in primary tumor and highest distribution was seen for Pattern III (53.3%), and least for Pattern V (0.00%). In secondary tumors, the predominant worst pattern was Pattern IV (50.0%) and least distribution was seen for Pattern I (0.00%). Connective tissue status for both primary and secondary tumors showed the predominance of loose type (85.2% and 79.2%) and least was variable type (0.8% and 0.6%), respectively. Status of inflammation in the primary tumor group showed a predominance of moderate grade of inflammation (50.0%) and very mild grade of inflammation (6.6%) was the least type. In the secondary tumor group, moderate grade (43.5%) of inflammation was predominant and very mild grade (5.4%) was the least. All the parameters showed a statistically significant difference on the application of Fisher's exact test between the two groups.Conclusion:Our study showed that POI could serve as an individual prognostic marker irrespective of the histologic differentiation of tumor. Tumor desmoplasia could be considered as an important reflection of the tumor-host interaction, especially in aggressive cancers. Host immune defense, especially tumor infiltrating lymphocytes must be noted as critical factors related to survival rate in OSCC patients. Assessment of mentioned parameters may lead to sound prognostic assessment and appropriate treatment planning thus reducing the possibility of recurrence or relapse. Hence, the parameters evaluated in our study could serve as independent or interdependent prognostic markers.

Predictive Significance of Tumor Grade Using 256-Slice CT Whole-Tumor Perfusion Imaging in Colorectal Adenocarcinoma

The preoperative assessment of tumor grade has important clinical implications for the treatment and prognosis of patients with colorectal adenocarcinomas. The purpose of this study is to investigate the predictive significance of colorectal adenocarcinoma grade using 256-slice whole-tumor computed tomography (CT) perfusion. Fifty-three patients with proven colorectal adenocarcinomas were enrolled. All of them underwent 256-slice whole-tumor CT perfusion. They were divided into two different subgroups according to postoperative pathological results: low grade and high grade. The Kruskal-Wallis test or one-way analysis of variance was used for comparison of CT perfusion parameters between different tumor grades. Multivariant correlation between pathologic tumor stage, histologic tumor differentiation, and whole-tumor CT perfusion parameters was evaluated by Spearman rank correlation coefficient. According to receiver operating characteristic (ROC) curves, perfusion parameters including blood flow (BF), peak enhancement index (PEI), blood volume (BV), and time to peak (TTP) of 53 patients were analyzed, and the sensitivity, specificity, and accuracy of these parameters in predicting tumor grade were calculated. There were significant differences in BF and TTP between low-grade and high-grade tumors. According to the ROC curve, BF and TTP were of diagnostic significance, with the area under the curve values of 0.828 and 0.736, respectively. The diagnostic threshold of BF was 32.12 mL/min/100 g and that of TTP was 18.10 seconds. The CT perfusion parameters (BF, TTP) of first-pass 256-slice whole-tumor CT perfusion imaging can reflect tumor grade in colorectal adenocarcinoma.

NF45 overexpression is associated with poor prognosis and enhanced cell proliferation of pancreatic ductal adenocarcinoma.

NF45, also referred to as nuclear factor of activated T cells, has been reported to promote the progression of multiple cancer types. However, the expression and physiological significance of NF45 in pancreatic ductal adenocarcinoma (PDAC) remain largely elusive. In this study, we investigated the clinical relevance and potential role of NF45 expression in PDAC development. Western blot analysis revealed that NF45 was remarkably upregulated in PDAC tissues, compared with the adjacent non-tumorous ones. In addition, the expression of NF45 in 122 patients with PDAC was evaluated using immunohistochemistry. In this way, we found that NF45 was abundantly expressed in PDAC tissues, and the expression of NF45 was correlated with tumor size (p = 0.007), histological differentiation (p = 0.033), and TNM stage (p = 0.001). Importantly, patients with low levels of NF45 expression exhibited better postoperative prognosis as compared with those with high NF45 expression. Furthermore, using PDAC cell cultures, we found that interference of NF45 expression using siRNA oligos suppressed PDAC cell proliferation and retarded cell cycle progression. Moreover, depletion of NF45 impaired the levels of cellular cyclin E and proliferating cell nuclear antigen (PCNA). Conversely, overexpression of NF45 facilitated the cell growth and accelerated cell cycle progression. Our results establish NF45 as an important indicator of PDAC prognosis with potential utility as a therapeutic target in this lethal disease.

High expression of ErbB3 binding protein 1 (EBP1) predicts poor prognosis of pancreatic ductal adenocarcinoma (PDAC).

Recent studies have identified that ErbB3 binding protein 1 (EBP1) is broadly expressed in various cancer tissues and critically involved in plenty of biological processes in this regard. However, the functional role of EBP1 in pancreatic ductal adenocarcinoma (PDAC) has never been elucidated. In this study, we found that EBP1 could serve as a prognostic biomarker of PDAC. Western blot analysis revealed that EBP1 was remarkably upregulated in PDAC tissues and cell lines. Using immunohistochemical analysis, we showed that the expression of EBP1 was correlated with tumor size (P = 0.004), histological differentiation (P = 0.041), and tumor node metastasis (TNM) stage (P = 0.000). Notably, Kaplan-Meier curve showed that high expression of EBP1 predicted significantly worsened prognosis of PDAC patients (P = 0.001). In addition, knockdown of EBP1 expression suppressed PDAC cell proliferation and retarded cell cycle progression. Furthermore, depletion of EBP1 induced the apoptosis of Panc-1 cells. Of great interest, we found that EBP1 interacted with anti-apoptotic protein, Bcl-xL, and promoted its accumulation. In summary, our results suggest that EBP1 is a novel prognostic indicator and potential therapeutic target of PDAC, shedding new insights into the important role of EBP1 in cancer development.

Histopathological differentiation of oral squamous cell carcinoma and salivary lactate dehydrogenase: A biochemical study.

Context:Early diagnosis of oral cancer is a priority health objective, in which oral health professionals may play a pivotal role. Detection should lead to less damage from cancer therapy and to a better prognosis.Aims:The aim was to estimate and compare the salivary lactate dehydrogenase (LDH) levels in various histological differentiation of oral squamous cell carcinoma (OSCC) patients and normal subjects.Settings and Design:Hospital-based setting, case-control study.Subjects and Methods:A case–control study was undertaken comprising 30 OSCC patients and 30 healthy controls. The OSCC patients were grouped into well-differentiated, moderately differentiated and poorly differentiated OSCC based on their histological tumor differentiation. Unstimulated whole saliva was collected, assayed for LDH levels using a standard kit and measured spectrophotometrically at 340 nm.Statistical Analysis Used:The results obtained were subjected to statistical analysis using Kruskal–Wallis and Mann–Whitney U-tests. Spearman's correlation was used to correlate the histological tumor differentiation with the salivary LDH levels.Results:The mean salivary LDH levels in the control group, well-differentiated OSCC group, moderately differentiated OSCC group, and poorly differentiated OSCC group were 117.33 ± 19.37 IU/L, 355.83 ± 16.73 IU/L, 484.18 ± 25.84 IU/L, and 620.35 ± 18.69 IU/L, respectively. The difference in the mean salivary LDH levels was statistically significant among the various groups (Kruskal–Wallis χ2 = 50.820, P < 0.001). Spearman's correlation showed significant difference between salivary LDH levels and histological differentiation of OSCC (r = −0.689, P < 0.01).Conclusions:The salivary LDH levels were higher in OSCC patients when compared to the healthy controls. The salivary LDH levels were found to be the highest among the poorly differentiated OSCC.

Relationship between histopathologic characteristics and epidermal growth factor receptor mutation in lung adenocarcinoma

To correlate morphological features with mutations of epidermal growth factor receptor (EGFR) in lung adenocarcinomas. According to 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society International Multidisciplinary Lung Adenocarcinoma Classification, a total of 72 surgically resected lung adenocarcinomas were collected and classified into different histological subtypes and different cell types (hobnail, columnar and polygonal). EGFR gene mutation was detected with the amplification refractory mutation method provided by the EGFR mutation test kit. The correlation between these subtypes and EGFR mutations were evaluated. Mutations of EGFR were detected in 48.6% (35/72) of lung adenocarcinomas; 19del and L858R were major mutational types (88.6%, 31/35). EGFR mutations were associated with female gender, non-smoking status, and well to moderately differentiated tumor histology. EGFR mutation types were not associated with age, smoking index, lymph node metastasis, stage, status of whether have or not have inclusion bodies or psammoma bodies and mitotic level. Correlations were observed between acinar and papillary adenocarcinoma subtypes and EGFR mutations according to the new classification. EGFR mutation was rare in the subtype of solid adenocarcinoma with mucin production and almost never observed in special subtypes (mainly mucinous and colloid adenocarcinoma). In addition, EGFR mutation was associated with the hobnail cell type. Lung adenocarcinomas of predominate acinar and papillary histological subtypes with hobnail cell morphology are good predictors for EGFR mutations.

Level and Evaluation of Tumor Marker CA-125 in Ovarian Cancer Patients in Khyber Pakhtunkhwa, Pakistan

Due to the increase in morbidity and mortality rate, cancer has become an alarming threat to the human population worldwide. Since cancer is a progressive disorder, timely diagnosis is necessary to prevent/stop cancer from progressing to a severe stage. In Khyber Paktunkhwa, Pakistan, many tumors are diagnosed with endoscopy and biopsy; rare studies exist regarding the diagnosis and evaluation of ovarian cancer, based on tumor markers like CA-125. The objectives of this study were to investigate and evaluate levels of CA-125 in hospitalized ovarian cancer patients. In this study, a total of 63 admitted patients having ovarian cancer by biopsy were included. The level of CA-125 was determined in the blood of these patients using ELISA technique. Out of 63 patients, the level of CA-125 was high in 52% . The affected individuals were more in the group of 40-60 and the level of CA-125 was comparatively higher in patients having moderately differentiated histology than those having well differentiated and poorly differentiated tumor histology. Moreover, the highest level of CA-125 was present among the patients having serous subtype of carcinoma and the common stage of carcinoma was stage II followed by stage III, I and IV. CA-125 level was high in more than 50% of the total patients. Moreover, CA-125 elevation was more common in serous subtype and stage II cancer patients.

Relationship among mismatch repair deficiency, CDX2 loss, p53 and E-cadherin in colon carcinoma and suitability of using a double panel of mismatch repair proteins by immunohistochemistry.

Biomarkers such as mismatch repair proteins, CDX2, p53, and E-cadherin are blamed for colon cancers, but the relationships of these biomarkers with each other and with pathological risk factors in colon carcinoma are still not clear. The aim of this study was to evaluate the association of these biomarkers with each other by using immunohistochemical staining and to compare their expression with pathological risk factors for colonic adenocarcinoma. We also aimed to study the usability of a double panel of mismatch repair proteins. One hundred and eleven cases with colonic adenocarcinoma were examined. There was a statistically significant relationship between tumor histological differentiation and perineural invasion, vascular invasion, mismatch repair deficiency, p53, CDX2, and E-cadherin (p < 0.05). PMS2 and MSH6 loss covered 100% of cases with mismatch repair deficiency. Mismatch repair deficiency was correlated with CDX2 loss and E-cadherin expression (p < 0.05). It was also observed that cases with PMS2 loss covered all the cases with CDX2 loss. In conclusion, this double panel may be used instead of a quadruple panel for detecting mismatch repair deficiency. Association of CDX2 and PMS2 in the present study is necessary to conduct further genetic and pathological studies focusing on these two markers together.

Podoplanin expression is correlated with the prognosis of lung squamous cell carcinoma.

Podoplanin is a 38 kDa transmembrane protein that is involved in cell migration and cancer cell invasion. Some studies have reported that podoplanin expression was correlated with poor prognosis in lung squamous cell carcinoma (SqCC). However, there have been no clinicopathological studies of podoplanin membrane expression and localization in lung SqCC. In this study, we focused on the intensity and localization of podoplanin membrane expression, and its clinicopathological significance for lung SqCC. Strong membrane expression of podoplanin was significantly associated with lymph node metastasis, lymphatic invasion, and histological differentiation. Cases with strong podoplanin expression at cell membrane showed better prognosis of lung SqCC (HR, 3.301). Peripheral localization of podoplanin was associated with tumor size, lymphatic invasion, and histological differentiation. Cases with peripheral podoplanin expression showed favorable prognosis of lung SqCC (HR, 2.830). Both strong membrane expression and peripheral expression of podoplanin were independent predictors of mortality of lung SqCC (HR, 2.869; HR, 2.443, respectively). The cases with strong or peripheral podoplanin expression showed better overall survival (P = 0.001, both). Podoplanin intensity is significantly associated with podoplanin localization (P < 0.001), and its correlation coefficient was 0.678. We concluded that podoplanin membrane expression, not only its localization, is a useful prognostic indicator of lung SqCC patients.