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Incidental detection of lymphoma in lymph node (LN) dissection for carcinoma is extremely rare. The occurrence and clinicopathological features of this rare condition have not been characterised. The medical records of 11,889 consecutive patients who underwent LN dissection for carcinoma in the abdominopelvic cavity were retrospectively reviewed. Among these patients, 11 had lymphomas detected in LN dissections and 7 had no previous history of lymphoma, representing an incidental detection rate of 0.06% (7/11889). The patients had a median age of 63 years (range, 48-69 years), and the male-to-female ratio was 1:2.5. The sites and histological types of the carcinoma were as follows: adenocarcinoma of the sigmoid colon (2 cases), endometrioid adenocarcinoma of the endometrium (2 cases), squamous carcinoma of the uterine cervix (1 case), adenocarcinoma of the stomach (1 case), and adenocarcinoma of the rectum (1 case). All incidental lymphoma cases (100%, 7/7) were low-grade B cell non-Hodgkin lymphoma (B-NHL), including 5 cases of follicular lymphoma (grades 1-2) and 2 cases of small lymphocytic lymphoma. The median follow-up interval was 39 months (5-65 months). All the patients were alive at the end of the follow-up period. Low-grade B-NHL can be incidentally detected during LN dissection for carcinoma in the abdominopelvic cavity. The subtype of incidental lymphoma is likely related to the epidemiology of lymphoma classes in the corresponding area. We should be aware of simultaneous occurrence of incidental lymphoma during lymphadenectomy for carcinoma.

The objective of the present study was to investigate the association between zinc finger protein (ZNF) 689 expression and the clinicopathological features and prognosis of hepatocellular carcinoma (HCC). A total of 102 paired HCC and paired non-cancerous tissues, and 16 normal liver tissues were collected. ZNF689 expression was examined in HCC tissues, paired-noncancerous tissues, and normal liver tissues using RT-qPCR and immunohistochemistry analysis, and the association between ZNF689 expression and HCC prognosis was analyzed using the Kaplan-Meier method. ZNF689 expression was not significantly different between HCC tissues and paired-noncancerous tissues (P=0.61). ZNF689 expression in HCC and paired-noncancerous tissues was significantly increased compared with that in normal liver tissues (P<0.01). Positive expression of ZNF689 protein in HCC was significantly associated with a tumor size of ≥10 cm, tumor capsule infiltration, and microvascular invasion (P<0.05). Positive expression of ZNF689 was a prognostic factor for overall survival time [hazard ratio (HR):1.961; P=0.048] and progression-free survival time (HR:1.902; P=0.041). ZNF689 maybe a novel predictor for prognosis of patients with HCC.

To investigate the clinicopathological features and prognostic factors of primary anorectal melanoma, we described the clinical presentations, histopathology, and prognosis of 60 cases in China. Patients' age ranged from 17 to 86 years, with a female-to-male ratio of 2.33:1. The prevalent anatomic site of tumor was the anorectum. The mean tumor thickness was 11.5 mm, and mean tumor size was 2.9 cm. Abdominoperineal resection was performed on 38 (63.3%) patients, whereas wide local excision was performed on 22 (36.7%) patients. Thirty-three (55.0%) patients were pathologically confirmed to have lymph node metastasis, and 9 (15%) patients had clinically distant metastasis at diagnosis. Histologically, epithelioid cell (91.7%) was the predominant cell type, followed by spindle (31.7%), pleomorphic (25.0%), and small round cell (5.0%). Solid sheet, nest, pseudopapillary, and pseudoalveolar growth patterns were noted in 45 (75.0%), 22 (36.7%), 13 (21.7%), and 6 (10.0%) cases, respectively. After a median follow-up of 44 months, the 5-year disease-specific survival rate was 33.3%. Age, tumor size, depth of invasion, tumor thickness, lymphatic metastasis, and lymphovascular and perineural invasion were significantly correlated with survival in univariate analysis. Multivariate analysis revealed that age greater than 70 years and tumor invasion beyond deep muscular layer/sphincter ani externus were independent poor prognostic factors. As the largest single-institution study of anorectal melanoma in an Asian population, we concluded that anorectal melanoma is a rare and lethal malignant neoplasm with morphologic diversity. Large population-based studies are still needed to establish an efficient staging system in evaluation of prognosis and facilitation of treatment for anorectal melanoma patients., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Patients with early stage lung cancer seldom present initial respiratory symptoms, causing a delayed diagnosis and missed opportunity to receive operation. This study aimed to investigate the prevalence of initial respiratory symptoms and identity what factors would predispose lung cancer patients to present initial respiratory symptoms in patients undergoing lung cancer surgery. Methods: A retrospective chart review was conducted on 3,203 patients undergoing surgery for primary lung cancer. The prevalence of initial respiratory symptoms was investigated and the comparisons of clinicopathological parameters were performed between patients with and without initial respiratory symptoms or between patients with single and multiple initial respiratory symptoms. Independent risk factors for presenting initial respiratory symptoms or multiple initial respiratory symptoms were identified using a logistic regression. Results: A total of 1,474 (46.0%) patients with lung cancer were admitted to hospital due to present initial respiratory symptoms. Symptom clusters of cough or sputum (33.1%) and bloody sputum or hemoptysis (16.7%) presented as the two major chief complaints for medical consultation while chest pain (6.9%) and chest distress or dyspnea (5.6%) remained relatively unusual. Multiple analyses found that coexisting chronic obstructive pulmonary disease (OR=1.70, 95% CI=1.41-2.05), tumor size >3 cm (OR=2.27, 95% CI=1.93-2.67), squamous cell carcinoma (OR=2.22, 95% CI=1.86-2.65), tumor located in left lower lung (OR=1.39, 95% CI=1.10-1.74) and advanced tumor stage (OR=1.27, 95% CI=1.06-1.52) were independent risk factors for presenting initial respiratory symptoms. Furthermore, current smoking (OR=1.36, 95% CI=1.07-1.73), tumor size >3 cm (OR=1.53, 95% CI=1.21-1.93) and squamous cell carcinoma (OR=1.68, 95% CI=1.32-2.15) were demonstrated to be independent risk factors for presenting multiple initial respiratory symptoms. Conclusions: Presenting initial respiratory symptoms was the common cause for medical consultation in patients undergoing lung cancer surgery. Patients with lung cancer in larger tumor size or squamous cell carcinoma more likely presented initial and even multiple initial respiratory symptoms., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Background and Aims: Recently, the abnormal expression of FoxM1 has been found in many malignant tumors. However, the clinicopathological and prognostic value of FoxM1 expression in hepatocellular carcinoma (HCC) patients remains controversial. We conducted a meta-analysis to establish the relationship between FoxM1 expression and the clinicopathological features and prognostic value in patients with HCC., Methods: An electronic search for relevant articles was conducted according to a set of criteria in the PubMed, Cochrane Library, Web of Science, EMBASE, Chinese CNKI and Chinese WanFang databases. The correlation data between FoxM1 expression and clinicopathological features and survival outcomes were analyzed. Pooled odds ratios (ORs) and hazard ratios (HRs) with 95% CIs were calculated using STATA14.2., Results: A total of 14 studies comprising of 2,036 patients were enrolled in this meta-analysis. The results showed that FoxM1 expression was related to the incidence, tumor size (>5 cm), vascular invasion, differentiation and TNM stage. Moreover, overexpression of FoxM1 indicated a poor 3- and 5-year overall survival rate (OS) and recurrence-free survival rate (disease-free survival rate)., Conclusion: Our meta-analysis indicated that FoxM1 expression was associated with incidence, tumor size (>5 cm), vascular invasion, differentiation and TNM stage. Accordingly, FoxM1 may be a reliable prognostic biomarker for patients with HCC. However, additional high-quality studies are still needed to further support these findings., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: Kidney cancer is one of the most common cancers in the USA causing 14,400 deaths per year. The phosphatase and tensin homolog (PTEN) has been extensively documented as a tumor suppresser gene in cancer. However, there is unclear evidence for its clinicopathological and prognostic role in kidney cancer., Methods: A systematic review of literature assessing PTEN expression and clinical outcome in patients with kidney cancer. Web of Science, PubMed, Embase, and Chinese databases were searched for collecting for the eligible studies providing sufficient information. Pooled odds ratios (ORs) and hazard ratios (HRs) were respectively used to evaluate the association between PTEN levels and the clinicopathological features and clinical outcomes., Results: A total of 35 studies enrolling 4532 patients were finally included in this study. For the survival outcome, the result suggested that shorter overall survival (OS) was correlated with low PTEN expression (HR = 0.57, 95% CIs: 0.45-0.74, P < 0.0001). The meta-analysis indicated a significantly increased risk of tumorigenesis in the PTEN low-level group relative to the control group (OR = 0.098, 95% CIs: 0.067-0.143, P < 0.001). Moreover, the results displayed the positive correlation between poorer differentiation (OR = 0.234, 95% CIs: 0.133-0.410, P < 0.001), distant metastasis (OR = 0.179, 95% CIs: 0.092-0.350, P = 0.001), lymph node metastasis (OR = 0.252, 95% CIs: 0.113-0.563, P < 0.001), advanced clinical stages (OR = 0.233, 95% CI: 0.133, 0.406, P < 0.001) and low PTEN expression. Finally, there was no obvious publication bias found in the meta-analysis., Conclusions: Decreased PTEN was associated with poorer survival outcomes of patients with kidney cancer and PTEN acts as a tumor suppressor in tumorigeneses and progression in kidney cancer., (Copyright © 2018. Published by Elsevier B.V.)

Columnar cell variant of papillary thyroid carcinoma (CCV-PTC) is an unusual neoplasm, the clinical behavior of which mainly depends on the encapsulation or infiltration. Patients with extensive extrathyroidal extension usually have an aggressive biological behavior. This study confirmed that beta-human chorionic gonadotropin (β-hCG) secreting invasive CCV-PTC has good prognosis comparing with a cohort of follicular cell differentiated thyroid carcinoma. On the contrary, positive immunoreaction with β-hCG was proved in three anaplastic thyroid carcinoma patients showing aggressive clinical courses. The clinicopathologic characteristics of CCV-PTC and the paraneoplastic syndromes in follicular cell differentiated thyroid carcinoma were further summarized using literature review., (© 2018 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.)

Background: Lung cancer is often complicated with chronic obstructive pulmonary disease (COPD). Coexistence of COPD has significant impacts on the decision-making process for lung cancer surgery as well as the postoperative effects. This study aimed to investigate the status of coexisting COPD and analyze its clinicopathological characteristics in lung cancer patients undergoing surgical resection., Methods: Clinical data of 3,006 patients with resected primary lung cancer from January 2008 to April 2014 were analyzed. Status of coexisting COPD was evaluated according to patient's lung function. Differences of clinicopathological characteristics between the COPD group and the non-COPD group were compared., Results: A total of 643 patients (21.4%) were complicated with COPD. The average age of patients with COPD (64.9±8.5 years) was significantly older than those without COPD (59.4±9.9 years). The percentage of males (85.7% vs. 54.0%) and current smokers (43.4% vs. 22.5%) were both higher in the COPD group than the non-COPD group (P<0.05). The percentage of patients with initial symptoms was higher in the COPD group than the non-COPD group (63.9% vs. 44.5%, P<0.05). The average white blood cell count was higher in the COPD group than the non-COPD group [(6.72±2.28 vs. 6.28±2.24) ×10 9 /L, P<0.05]. The percentage of tumor size more than 3 cm was higher in the COPD group than the non-COPD group (53.2% vs. 38.0%, P<0.05). Squamous cell carcinoma accounted for 47.6% in the COPD group while adenocarcinoma accounted for 72.4% in the non-COPD group (P<0.05). A higher percentage of lung cancer with poor differentiation was found in the COPD group than the non-COPD group (53.2% vs. 43.6%, P<0.05). The median total and postoperative length of hospital stay were significantly longer in the COPD group than the non-COPD group (13 vs. 11 days, 8 vs. 7 days, respectively, P<0.05)., Conclusions: COPD is a common comorbidity of early stage lung cancer. Lung cancer patients with coexistence of COPD have obviously different clinicopathological features compared to patients without COPD, which requires special attention and management during the perioperative period of lung cancer., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Monoamine oxidase A (MAOA), a mitochondrial enzyme, is closely associated with neurological disorders. Recently, MAOA has been linked to the progression of prostate cancer, hepatocellular carcinoma, and cholangiocarcinoma. However, MAOA was reported to have different effects on the progression of these types of cancer, and the role of MAOA in non-small cell lung cancer (NSCLC) progression remains unclear. The present study determined the expression of MAOA and epithelial to mesenchymal transition (EMT) markers in 45 pairs of NSCLC and matched non-tumor adjacent lung tissues, and further analyzed the correlation between MAOA expression and the EMT or the development of clinicopathological features. The results demonstrated that protein and mRNA expression levels of MAOA in NSCLC tissues were higher than those observed in the matched non-tumor adjacent lung tissues. Furthermore, the increased MAOA expression in NSCLC tissues was positively correlated with N-cadherin ( r =0.525, P=0.002), Slug ( r =0.515, P=0.001), and Twist ( r =0.448, P=0.008) expressions, but negatively correlated with E-cadherin expression ( r =-0.387, P=0.01). Additionally, the elevated MAOA expression in NSCLC tissues was associated with late stage NSCLC (Z=-2.596, P=0.029) and lymph node metastases (Z=-2.378, P=0.020). These findings suggest that MAOA may have a role in promoting NSCLC progression by mediating EMT.

This case-control study aims to investigate the correlations of insulin-like growth factor receptor 1 (IGF-1R) and cyclooxygenase 2 (COX-2) expressions with Ras and BRAF genetic mutations, clinicopathological features and prognosis of colorectal cancer (CRC) patients. A total of 213 CRC patients (case group) and 200 healthy individuals (control group) were selected from our hospital. Ras (K-Ras/N-Ras) and BRAF genetic mutations were detected by direct sequencing. The positive expression rates of IGF-IR and COX-2 in CRC and normal tissues were detected using immunohistochemistry. RT-qPCR and Western blotting were applied to detect the mRNA and protein expressions of IGF-IR and COX-2 in CRC tissues and normal tissues. Total mutation rate of N-Ras, BRAF and K-Ras in case group were 5.2%, 12.2% and 47.4%, respectively. The expressions of IGF-IR and COX-2 were higher in CRC tissues with Ras and BRAF mutations than in those without. CRC tissues with Ras mutation showed higher COX-2 expression than those with BRAF mutation. IGF-IR and COX-2 expressions were correlated to infiltration degree, lymphatic metastasis (in CRC tissues with and without Ras and BRAF mutations), and Dukes stages (only in CRC tissues with Ras and BRAF mutations). CRC patients with negative expressions of IGF-IR and COX-2 had significantly higher accumulative survival rate and longer mean survival duration than those with positive expressions of IGF-IR and COX-2. These findings indicate that IGF-1R and COX-2 expressions may be associated with Ras and BRAF genetic mutations, clinicopathological feature and prognosis of CRC patients.

Background: Breast cancer (BC) displays different clinicopathological features and outcomes based on patient age, molecular subtype, and treatment. However, such features in BC patients in northwest China are unclear. This study investigated the clinicopathological features and overall survival (OS) of early stage BC patients using a population-based study., Methods: Patients who were newly diagnosed with BC at the First Affiliated Hospital of Xi'an Jiaotong University between January 2001 and June 2012 were included. Clinicopathological features and OS were assessed., Results: The median age of 1287 patients was 50 years, with an average tumor size of 2.65 cm. Additionally, 42.7% were luminal A, 25.6% luminal B, 9.3% Her2 overexpression, and 17.7% triple negative. The cut-off age was 35 years, and young patients (< 35) tended to have larger tumors, ≥ 4 positive lymph nodes, grade 2 or 3 histology, non-luminal types, high Ki67, and poor outcomes. Patients with luminal A tumors showed moderate features: 50.6% had tumors < 2 cm, 56.7% had negative lymph nodes. Patients with Her2 overexpression tumors showed aggressive features and the poorest survival (5-year OS 67.6%). Patients with triple negative tumors were the youngest (average 48.4 years), but had the largest proportion of grade 3 histology and poor outcomes., Conclusion: Our results are consistent with those in other provinces in China, but showed an earlier age at diagnosis and more aggressive pathological features compared to developed countries. Additionally, each molecular subtype showed specific features and different survival outcomes., (© 2017 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: Yes-associated protein (YAP) overexpression is reported to be associated with risk of hepatocellular carcinoma (HCC) but current studies have not explored the relationship between YAP expression with HCC clinicopathological features., Methods: To assess these associations, a meta-analysis was performed which included four eligible studies including 391 HCC cases and 334 controls. There were eight eligible studies to investigate the association between YAP expression in HCC and clinicopathological features of liver cancer patients. Literature was obtained from PubMed, Embase, Wangfang and China National Knowledge Infrastructure., Results: Analysis indicated that YAP expression in HCC was greater than in adjacent non-tumour tissue (odds ratio [OR], 15.80, 95% confidence interval [CI], 10.53-23.70, P<.00001; heterogeneity=.30). YAP overexpression in HCC was significantly associated with vascular invasion (OR, 2.21, 95% CI, 11.64-2.97, P<.00001, heterogeneity=.10), less cellular differentiation (OR, 2.38, 95% CI, 1.61-3.51, P<.00001, heterogeneity=.333), tumours larger than 5 cm (OR, 2.52, 95% CI, 1.75-3.62, P<.00001; heterogeneity=.17) and TNM tumour stage I + II (OR, 0.44, 95% CI, 0.28-0.75, P=.00003, heterogeneity=.12)., Conclusions: Overexpression of YAP contributes to HCC formation, and its overexpression is associated with vascular invasion, low cellular differentiation tumours larger than 5 cm and TNM tumour stage III + IV., (© 2017 The Authors. Liver International Published by John Wiley & Sons Ltd.)

Aims and Background: Discs large homolog 1 (DLG1) belongs to the modular proteins Membrane Associated Guanylate Kinases (MAGUKs) and plays a major role in the formation of cell-cell junctions and cell polarity. DLG1 varies in expression and localization among malignancies. However, the clinical significance of DLG1 in the context of human colorectal cancer (CRC) remains unclear. The purpose of this study study is to determine the association of DLG1 with clinicopathological characteristics and prognosis of CRC patients., Methods: DLG1 expression in human CRC was detected by immunohistochemical analysis and validated with mRNA data from a high-throughput sequencing TCGA datasets. The association of DLG1 expression with clinicopathological features in CRC patients was then statistically analyzed., Results: Immunohistochemistry analysis found that DLG1 expression was significantly elevated in CRC tissues, compared with the expression in adjacent non-cancerous colon tissues ( P =0.000). High DLG1 expression was significantly associated with advanced clinical stage ( P =0.011) and enhanced tumor invasion ( P =0.002). The TCGA mRNA expression data revealed that DLG1 mRNA expression was up-regulated in CRC tissues with advanced clinical stage ( P =0.008), enhanced tumor invasion ( P =0.042), lymph node metastasis ( P =0.030), and distant metastasis ( P =0.043). Kaplan-Meier survival curves revealed that CRC patients with high DLG1 levels had shorter survival (P=0.040). Furthermore, DLG1 was an independent prognostic factor for CRC patients (HR 2.202, 95% CI 1.057-4.587; P =0.035)., Conclusions: These findings suggest that the increased expression of DLG1 may be predictive of an unfavorable prognosis in CRC patient and serve as a novel therapeutic target in this malignancy., (© 2017 by the Association of Clinical Scientists, Inc.)

Previous studies indicated that microRNA (miR)-675 and its precursor lncRNA H19 were both overexpressed in glioma tissues, and H19 might play an oncogenic role. To investigate the involvement of miR-675 in gliomas and its underlying mechanisms, we here collected candidate target genes of miR-675-5p from miRTarBase (http://mirtarbase.mbc.nctu.edu.tw/, Release 6.0), which contains the experimentally validated microRNA-target interactions. Then, regulatory effects of miR-675 on its target genes were validated using clinical samples and glioma cell lines. Involvement of the miR-675-target axis deregulation in cell proliferation, migration and invasion of glioma was demonstrated by both gain- and loss-of-function experiments. As a result, retinoblastoma 1 (RB1) was identified as a candidate target gene of miR-675-5p. Expression levels of miR-675-5p in glioma tissues and cells were negatively correlated with RB1 expression at both mRNA and protein levels. Importantly, deregulation of the miR-675-5p-RB1 axis was significantly associated with advanced World Health Organization (WHO) grade and low Karnofsky performance score (KPS) score of glioma patients. Luciferase reporter assay verified that RB1 was a direct target gene of miR-675 in glioma cells. Functionally, miR-675 promoted glioma cell proliferation, migration and invasion. Notably, simulation of RB1 antagonized the effects induced by miR-675 up-regulation in glioma cells. In conclusion, our data suggest that miR-675 may be a key negative regulator of RB1 and the imbalance of the miR-675-RB1 axis may be clinically associated with aggressive progression of glioma patients. In addition, miR-675 may act as an oncogenic miRNA in glioma cells via regulating its target gene RB1., (Copyright © 2017 Elsevier Inc. All rights reserved.)

MicroRNA (miR)-375 has been reported to function as a tumor suppressor in gastric cancer via targeting Janus kinase 2 (JAK2). Until now, no clinical evidence of miR-375-JAK2 combination in gastric cancer has been documented. Here, quantitative real-time PCR was performed to detect the serum levels of miR-375 and JAK2 mRNA in 100 patients with gastric cancer and 50 healthy controls. Receiver operating characteristic (ROC) analysis was used to assess the predictive diagnostic value of serum miR-375 and/or JAK2 mRNA for gastric cancer. Associations of serum miR-375 and/or JAK2 mRNA levels with various clinicopathological features and prognosis in patients with gastric cancer were also analyzed. As a result, miR-375 expression was significantly downregulated, while JAK2 mRNA expression was dramatically upregulated, in patients' sera of gastric cancer (both P<0.001), compared to healthy controls. Notably, the areas under ROC curve for serum miR-375 and JAK2 discriminating gastric cancer patients from healthy controls were respectively 0.871 (sensitivity = 82.00%, specificity = 72.00%) and 0.864 (sensitivity = 55.00%, specificity = 100.00%). Moreover, miR-375 downregulation and/or JAK2 upregulation were all significantly associated with positive lymph node metastasis, high tumor-node-metastasis stage and the presence of H. pylori infection in patients with gastric cancer (all P<0.05). Furthermore, serum miR-375 and/or JAK2 were all independent prognostic factors for patients with gastric cancer. Importantly, the prognostic value of miR-375-JAK2 combination was more significant than considered alone. Collectively, serum miR-375 and JAK2 combination may be a potential diagnostic and prognostic predictor of gastric cancer. miR-375-JAK2 axis might be a promising candidate for a molecular targeted therapy of this malignancy., Competing Interests: None., (IJCEP Copyright © 2017.)

Background: Numerous studies have shown that plasma fibrinogen was linked to esophageal cancer (EC) risk. However, the clinical significance of plasma fibrinogen in EC patients remain unclear and need to be further clarified., Results: A total of 2865 patients with EC from 11 published studies were included in this meta-analysis. The prognostic and clinical relevance of plasma fibrinogen were evaluated in EC patients. Statistical significance of the pooled hazard ratio (HR) was found for overall survival (OS), disease free survival (DFS) and recurrence-free survival (RFS) in EC. Subgroup analyses for OS were also performed to confirm the prognostic value of plasma fibrinogen. Additionally, the overall results indicated that elevated plasma fibrinogen was significantly associated with tumor invasion, lymph node metastasis (LNM) and clinical stage., Materials and Methods: A comprehensive literature retrieval was performed in PubMed, Embase, Cochrane database, Web of science and Chinese National Knowledge Infrastructure (CNKI) and Wanfang databases to identify relevant studies published prior to April 15, 2017., Conclusions: Elevated plasma fibrinogen could be served as a promising biomarker for predicting a poor prognosis and unfavorable clinicopathologic features for EC., Competing Interests: CONFLICTS OF INTEREST The authors declared no conflicts of interest.

Purpose: The present study aimed to explore the survival outcomes of patients with colorectal cancer (CRC) aged 35 years and younger., Methods: This retrospective cohort study included a total of 995 patients with CRC treated between January 2003 and September 2011. The patients were assorted into the young (aged 18-35 years) and older (aged 36-75 years) groups. The clinical characteristics and survival outcomes of the patients in the young group were compared with those of the patients in the older group for evaluation., Results: Compared with the older group, a significantly higher number of patients in the young group had right-sided colon cancer (30.9 vs. 19.6%, P = 0.026), high histologic grade tumor (14.7 vs. 6.4%, P = 0.021), and stage III disease (50.0 vs. 35.5%, P = 0.016). In stage III disease, compared with the older group, the patients in the young group had worse survival outcome in terms of 5-year overall survival (OS, P = 0.007), cancer-specific survival (CSS, P = 0.010), and disease-free survival (DFS, P = 0.039). Multivariate analysis revealed that age ≤35 years was an independent risk factor in terms of 5-year OS (hazard ratio [HR] = 1.68; 95% confidence interval [CI]: 1.12-2.54; P = 0.012), CSS (HR = 1.74; 95% CI: 1.15-2.65; P = 0.009), and DFS (HR = 1.58; 95% CI: 1.06-2.35; P = 0.024)., Conclusions: The young patients with CRC aged 35 years and younger had worse prognosis compared with older patients, especially for stage III disease.

Despite tremendous efforts to develop curative agents, there are few effective drugs for the treatment of hepatocellular carcinoma (HCC). This is predominantly due to the variations in individual HCC cases. As numerous HCC cases have no mutations in known tumor-associated genes, identification of novel genes involved in the development and progression of human cancers is considered to be an urgent issue. In the present study, surgical specimens of HCC were analyzed for the expression patterns of ubiquitin-conjugating enzyme, cell division cycle 34 (CDC34), which is hypomethylated in its promoter region and exhibits elevated expression levels in mouse skin tumors. The results of the current study clearly indicated that the elevated CDC34 expression level in cancerous regions was significantly associated with favorable clinicopathological features, such as reduced alanine aminotransferase (ALT) levels and histological grades. Similarly, a higher T/N ratio, which is the ratio of CDC34 expression in HCCs to that in non-tumorous tissues, was significantly associated with favorable features, such as a lower indocyanin green retention rate after 15 min (ICG15R), reduced α-fetoprotein and smaller tumor size. These results indicate that the CDC34 expression level in HCC is a marker for predicting the HCC prognosis and that CDC34 acts as a tumor suppressor.

In patients with colorectal cancer (CRC), the BRAF V600E mutation has been reported to be associated with several clinicopathological features and poor survival. However, the prognostic implications of BRAF V600E mutation and the associated clinicopathological characteristics in CRCs remain controversial. Therefore, we reviewed various clinicopathological features, including BRAF status, in 349 primary CRCs and analyzed the relationship between BRAF status and various clinicopathological factors, including overall survival. Similar to previous studies conducted in Eastern countries, the incidence of the BRAF V600E mutation in the current study was relatively low (5.7%). BRAF-mutated CRC exhibits distinct clinicopathological features from wild-type BRAF-expressing cancer independent of the microsatellite instability (MSI) status. This mutation was significantly associated with a proximal tumor location (P = 0.002); mucinous, signet ring cell, and serrated tumor components (P < 0.001, P = 0.003, and P = 0.008, respectively); lymphovascular invasion (P = 0.004); a peritumoral lymphoid reaction (P = 0.009); tumor budding (P = 0.046); and peritoneal seeding (P = 0.012). In conclusion, the incidence of the BRAF V600E mutation was relatively low in this study. BRAF-mutated CRCs exhibited some clinicopathological features which were also frequently observed in MSI-H CRCs, such as a proximal location; mucinous, signet ring cell, and serrated components; and marked peritumoral lymphoid reactions., Competing Interests: The authors have no potential conflicts of interest to disclose.

Incidental papillary thyroid carcinomas (IPTCs) consist of a significant portion of increasing incidence in papillary thyroid carcinomas. This study investigated the clinicopathological features of IPTCs from different perspectives and by comparing nonincidental PTCs (NIPTCs) in patients who underwent total thyroidectomy and lymph node dissection. Basic results were as follows. IPTC was present in 27.9% of 308 patients. IPTCs were significantly accompanied by lymphocytic thyroiditis (LT), particularly, multinodular hyperplasia (MNH). IPTCs were more common in older patients (51.3 years vs. 47.2 years) and in female patients. IPTCs significantly differed from NIPTCs in terms of smaller tumour size, lymphatic vessel invasion (2.6% vs. 97.4%), extrathyroidal extension (4.3% vs. 95.7%), lymph node metastasis (3.6% vs. 96.4%), multifocality (21.2% vs. 78.8%), bilaterality (5.3% vs. 94.7%), and BRAFV600 mutation (6.7% vs. 93.3%). Older age, bilaterality, encapsulation, and radioactive iodine (RAI) were significantly more common in IPTCs > 5 mm than in those ≤ 5 mm. In conclusion, IPTCs are more commonly associated with LT and MNH. IPTCs may have a more favourable prognosis than NIPTCs, and tumour size > 5 mm may predict bilaterality and need for RAI. Nevertheless, the patient-based clinical approach in IPTCs may have benefits in the management of IPTCs.

Background: Clinical significance of microRNA (miR)-15a in human esophageal squamous cell carcinoma (ESCC) remains unclear., Objective: To evaluate the expression level of miR-15a and to determine its potential for diagnosis and prognosis in ESCC., Methods: Quantitative reverse transcription polymerase chain reaction was performed to examine the expression levels of miR-15a in ESCC tissues and patients' sera. The diagnostic and prognostic implications of serum miR-15a level in human ESCC were further evaluated., Results: Expression levels of miR-15a in ESCC tissues and patients' sera were significantly decreased (both P< 0.001). Additionally, serum miR-15a had an optimal diagnostic cut-off point (2.29) for ESCC with sensitivity of 86.36% and specificity of 100.00%. Moreover, low serum miR-15a level more frequently occurred in ESCC patients with advanced tumor-node-metastasis, T and N stages (all P= 0.01) and poor tumor differentiation (P= 0.03). The Kaplan-Meier curve showed that low miR-15a expression was significantly associated with shorter overall survival (OS) and disease-free survival (DFS) of ESCC patients (both P< 0.001). Further multivariate analysis identified miR-15a as an independent prognostic factor for both OS and DFS (both P= 0.01)., Conclusion: Decreased expression of miR-15a may play a crucial role in ESCC development and progression. Serum miR-15a level could be used as a potential diagnostic and prognostic marker in clinics.

MicroRNA (miRNA or miR)-298 has been reported to be downregulated and to modify the expression of the polycomb protein enhancer of zeste 2 (EZH2) in recurrent epithelial ovarian cancer (EOC). To date, no functional evidence of a miR-298-EZH2 axis in EOC has been documented. The present study aimed to investigate the associations of miR-298 and/or EZH2 expression with clinicopathological features of EOC patients, and revealed their roles in cell motility based on EOC cell lines. Reverse transcription-quantitative polymerase chain reaction was performed to detect the expression levels of miR-298 and EZH2 messenger RNA in human EOC tissues and cell lines. Wound healing and transwell assays were performed to determine the function of the miR-298-EZH2 axis on cell migration and invasion, respectively. Compared with normal tissues, miR-298 expression was significantly downregulated, while EZH2 expression was significantly upregulated, in human EOC tissues (both P=0.001). In addition, miR-298 downregulation and EZH2 upregulation were significantly associated with high clinical stage (both P=0.01) and pathological grade (both P=0.02) of EOC patients. Furthermore, the ectopic expression of miR-298 could efficiently inhibit cell migration and invasion. Notably, the overexpression of EZH2 could restore the cell migration and invasion abilities suppressed by miR-298. Our data offer convincing evidence that the dysregulation of the miR-298-EZH2 axis may be important in tumor progression of EOC patients. The present study also confirmed a tumor-suppressive role of miR-298 in modulating EOC cell motility by regulating the expression of EZH2, implying its potential as a novel miRNA-based therapeutic target for the treatment of human EOC.

Background: Lymphoepithelioma-like carcinoma (LELC) is a rare form of non-small cell lung carcinoma. The current study focused on its clinicopathological features and potential factors influencing the prognosis., Methods: The statistical analysis was based on the clinicopathological records and the prognosis of 43 LELC patients, analyzed by Kaplan-Meier method, Log-rank test, and COX regression analysis., Results: The patients' average age was 57.35±9.22 years, 86.05% of them were non-smokers and 53.49% were women. The average tumor diameter was 3.24±1.57 cm. The 2- and 5-year overall survival (OS) rates of LELC patients were 90% and 74%, respectively; the disease-free survival (DFS) rates were 87% and 47%, respectively. The patients with large tumor, accompanied with lymph nodes metastasis or at the advanced stage had the worst OS, and the patients with lymph nodes metastasis or at the advanced stage had the worst DFS. Univariate analysis indicated that T and N grading and TNM stage influenced the OS, and N grading and TNM stage influenced the DFS; the independent factors affecting OS or DFS were not identified by multivariate analysis., Conclusions: LELC commonly occurred in senior non-smoking women. In summary, the prognosis of LELC was satisfactory., Competing Interests: The authors have no conflicts of interest to declare.

Background: Mastermind-like transcriptional coactivator 1(MAML1) is a transcriptional coregulator of activators in various signaling pathways. High MAML1 was associated with tumorigenesis, progression, and aggressiveness in various tumors. The role of MAML in Hepatocellular Carcinoma (HCC), however, has not been directly addressed. The present study was to determine its association with clinicopathological characteristics and prognosis of HCC patients., Materials and Methods: MAML1 expression at protein level in human HCC and normal liver tissues was detected by immunohistochemistry analysis, which was further validated by high-throughput sequencing data TCGA dataset at mRNA level. Then, the association of MAML1 expression with clinicopathological features of HCC patients was statistically analyzed., Results: Immunohistochemistry analysis found that MAML1 expression was significantly increased in HCC tissues compared with those in normal tissues (P=0.005). High MAML1 was dramatically associated with advanced clinical stage (P=0.019) and enhanced tumor invasion (P=0.019). The TCGA mRNA expression data showed that MAML1 was upregulated in HCC with young age (P=0.005). Kaplan-Meier survival curves revealed that HCC patients with high MAML1 levels had shorter survival (P=0.040). Furthermore, high MAML1 expression was an independent prognostic factor for HCC patients (HR 1.841, 95% CI 1.045-3.243; P=0.035)., Conclusions: Our data suggests that MAML1 may play an important role in tumor progression of HCC. The increased expression of MAML1 may efficiently predict poor overall survival in HCC patients, and it may be a potential prognostic marker of this malignancy., (© 2016 by the Association of Clinical Scientists, Inc.)

Perivascular epithelioid cell tumor (PEComa) of the pancreas is an unusual tumor deriving from mesenchyma. This paper described a case of pancreatic PEComa, which was initially suspected as neuroendocrine carcinoma by biopsy, and therefore surgical treatment was recommended due to undetermined diagnosis. Examination of the surgical specimen under a microscope showed that the tumor cell's morphology was epithelioid or spindle-shaped, and ranged in a nested pattern. Additionally, these cells had a large extent of acidophilic cytoplasm, no mitotic figures, and expressed HMB-45, melan-p, and smooth muscle actin immunohistochemically. Pathological examination indicated that PEComa originated from the pancreas, but symptoms related to tuberous sclerosis were absent. Since PEComa is extremely rare in the pancreas, it is likely to be ignored in differential diagnosis. In conclusion, our article highlighted the clinicopathological features of PEComa, and we conducted a literature review focusing on PEComa so as to deepen the understanding of this tumor type.

The preoperative nutritional and immunological statuses have an important impact in predicting the survival outcome of patients with various types of malignant tumors. Our study aimed to explore the clinical significance and predictive prognostic potential of Onodera's prognostic nutritional index (PNI) in patients with colorectal carcinoma. This retrospective study included a total of 1321 patients who were diagnosed with colorectal cancer and who had been surgically treated between January 1994 and December 2007. The PNI level was determined according the following formula: 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (per mm(3)). The impact of PNI on clinicopathological features and overall survival (OS) was determined. The optimal cutoff value of PNI was set at 45. Patients in the low-PNI group had a greater potential to have aggressive histological features, advanced tumors (T), nodal involvement (N), metastasis (M), and TNM stage than those in the high-PNI group. The low-PNI group had a worse OS than the high-PNI group (5-year survival rate 56.1 vs 64.8 %, respectively; P < 0.05). Furthermore, the PNI value was an independent prognostic factor for colorectal cancer in this study. The OS was significantly lower in the low-PNI group than in the high-PNI group in patients with TNM stage II and III diseases. Preoperative PNI is a simple and useful marker to predict clinicopathological features and long-term survival outcome in patients with colorectal carcinoma. PNI analysis should be included in the routine assessment of patients with locally advanced colorectal cancer.

Our previous study demonstrated that enhancer of zeste homolog 2 (EZH2) overexpression may be associated with aggressive tumor progression and poor prognosis in human astrocytoma. The aim of this study was to investigate the underlying mechanisms of EZH2 on astrocytoma tumorigenesis. An online program miRWalk (http://www.umm.uni-heidelberg.de/apps/zmf/mirwalk/) was used to predict possible microRNAs (miRNAs) that might target EZH2 messenger RNA (mRNA). Then the functions of the miRNA-EZH2 mRNA axis in astrocytoma cell proliferation, invasion, and migration were also assessed. We further evaluated the clinical value of the miRNA-EZH2 mRNA axis in astrocytomas. As a result, we identified EZH2 as a target gene of miR-144. In addition, forced expression of miR-144 suppressed astrocytoma cell proliferation, invasion, and migration by down-regulating EZH2. Moreover, miR-144 down-regulation and EZH2 mRNA up-regulation were both significantly associated with advanced World Health Organization grades and low Karnofsky performance status score of astrocytoma patients. Importantly, survival analysis identified the combined expression of miR-144 and EZH2 (miR-144/EZH2) as an independent prognostic factor for overall survival in astrocytoma patients. In conclusion, miR-144 may function as a tumor suppressor by regulating EZH2 expression, and miR-144/EZH2 expression may be a highly sensitive marker for the prognosis in astrocytoma patients., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background and Purpose: To investigate the clinical significance of microRNA (miR)-23a and miR-23b expression in human gastric cancer (GC)., Methods: Quantitative RT-PCR was performed to detect the expression changes of miR-23a and miR-23b in 160 human GC tissues and paired normal mucosa. The associations between miR-23a and miR-23b expression, and the selected clinicopathological characteristics and patients' prognosis were also evaluated., Results: MiR-23a (GC vs. Normal: 3.98 ± 1.23 vs. 2.29 ± 1.12, P < 0.001) and miR-23b (GC vs. Normal: 3.70 ± 1.24 vs. 1.58 ± 1.18, P < 0.001) expression were both increased dramatically when compared with paired normal mucosa. Notably, the expression levels of miR-23a in GC tissues were positively correlated with those of miR-23b (Spearman correlation coefficient r = 0.77, P < 0.001). Then, the coexpression of miR-23a and miR-23b (miR-23a-high/miR-23b-high) in GC tissues was significantly associated with the advanced TNM stage (P < 0.001), the presence of lymph node metastasis (P = 0.008) and the great depth of invasion (P = 0.02). Furthermore, both univariate and multivariate analyses showed that miR-23a/miR-23b co-expression was an independent predictor for unfavorable overall survival., Conclusions: These results suggest that the dysregulation of miR-23a and miR-23b may be implicated in the progression of human GC. Combined expression of miR-23a and miR-23b appears to be a valuable marker for prognosis of this disease.

Salivary adenoid cystic carcinoma (SACC) is a common salivary malignancy. The current treatment option for SACC is complete surgical excision with postoperative radiotherapy. The prognosis remains unsatisfactory, due to frequent local recurrence and distant metastases that directly reduce the overall survival time. Previous studies have shown that overexpression of tumor-associated calcium signal transducer 2 (TACSTD2) is associated with poor prognosis in various human epithelial cancers. The expression of TACSTD2 in SACC is currently unknown. The present study therefore aimed to retrospectively investigate TACSTD2 protein expression by immunohistochemistry on paraffin-embedded primary tumor tissue samples from a series of consecutive SACC patients (n=81). The correlation of TACSTD2 expression with clinicopathological variables was evaluated using either the Kruskal-Wallis or Mann-Whitney statistical tests. The survival curves were plotted using the Kaplan-Meier method. The parameters of prognostic significance found by univariate analysis were verified in a multivariate Cox regression model. Overexpression of TACSTD2 was detected in 35/81 (44%) SACC patients and was significantly associated with a decreased overall survival (P<0.01). Univariate analysis showed that TACSTD2 overexpression was correlated with TNM stage (P=0.020), local recurrence (P=0.002) and distant metastasis (P=0.001). Multivariate analyses further revealed that TACSTD2 may be an independent prognostic indicator. In conclusion, TACTSD2 could be recognized as an independent prognostic indicator for SACC. Gene therapy targeting TACSTD2 may be a possible treatment approach for patients with SACC overexpressing this cell-surface marker.

Background: To clarify the involvement of HIVEP3 and SOX9 coexpression in prostate cancer (PCa)., Methods: A small interfering RNA was used to knockdown SOX9 expression in a PCa cell line and to analyze the effects of SOX9 inhibition on the expression of HIVEP3 in vitro. Then, HIVEP3 and SOX9 expression patterns in the human PCa tissues were detected using quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis and immunohistochemistry., Results: We found that the downregulation of SOX9 could inhibit the expression of HIVEP3 in the PCa cells in vitro. In addition, both HIVEP3 and SOX9 messenger RNA expression levels in the PCa tissues were significantly higher than those in the noncancerous prostate tissues (P=0.006 and P<0.001, respectively). Moreover, the immunohistochemical staining scores of HIVEP3 in the PCa tissues with PSA failure were significantly higher than those without (P=0.042); the increased SOX9 protein expression was more frequently found in the PCa tissues with a high Gleason score (P=0.045) and a high clinical stage (P=0.012). The tumors showing the HIVEP3-high/SOX9-high expression more frequently had PSA failure (P=0.024). When the patients with an HIVEP3 overexpression combined with the SOX9 overexpression, this group had a worse biochemical recurrence-free survival (P<0.001). Furthermore, the multivariate analysis showed that the HIVEP3/SOX9 coexpression was an independent predictor of an unfavorable biochemical recurrence-free survival., Conclusion: Our data offer the convincing evidence for the first time that a combined analysis of HIVEP3 and SOX9 may help to predict the tumor progression and prognosis of PCa patients. In particular, the overexpression of HIVEP3 in PCa might partly explain the poor prognosis of patients with an upregulation of SOX9.

Objective: To explore the relationship between peroxisome proliferator activated receptor-gamma (PPARγ) and peroxisome proliferator-activated receptor-gamma coactivator-1 (PGC-1) expression in gastric carcinoma (GC), and analyze their correlations with clinicopathological features and clinical outcomes of patients., Methods: The two-step immunohistochemical method was used to detect the expression of PPARγ and PGC-1 in 179 cases of GC, and 108 cases of matched normal gastric mucosa. Besides, 16 cases of fresh GC specimens and corresponding normal gastric mucosa were detected for PGC-1 expression with Western blotting., Results: The positive rates of PPARγ and PGC-1 expression were significantly lower in GC (54.75%, 49.16%) than in normal gastric mucosa (70.37%, 71.30%), respectively (P<0.05). The decreased expression of PGC-1 in GC was confirmed in our Western blot analysis (P=0.004). PPARγ and PGC-1 expressions were related to Lauren's types of GC (P<0.05). Positive correlation was found between PPARγ and PGC-1 expression in GC (rk=0.422, P<0.001). The survival time of PPARγ negative and positive patients was 36.6±3.0 vs. 38.5±2.7 months, and no statistical difference was found between the 5-year survival rates of two groups (34.4% vs. 44.1%, P=0.522, log-rank test); the survival time of PGC-1 negative and positive patients was 36.2±2.8 vs. 39.9±2.9 months, while no statistical difference was found between the 5-year survival rates of the two groups (32.0% vs. 48.2%, P=0.462, log-rank test)., Conclusions: Decreased expression of PPARγ and PGC-1 in GC was related to the Lauren's classification. Their expressions in GC were positively correlated, indicating that their functions in gastric carcinogenesis may be closely related.

Purpose: Gastric cancer (GC) remains a leading cause of death worldwide, and an elevated expression of osteopontin (OPN) may correlate with its poor survival. Alternative splicing of OPN can result in three isoforms, OPN-a, OPN-b and OPN-c. The aim of our current study is to examine the expression pattern and biological functions of OPN splice variants in GC., Methods: Firstly, we evaluated the expression of OPN splice variants in 7 gastric cell lines, 101 pairs of GC tissues and their adjacent non-tumor tissues by Quantative real-time PCR (QT-PCR). Gain-of-function experiments were subsequently performed to determine their diverse roles in malignant behaviors of GC. Besides, their differential effects on the regulation of crucial downstream molecules were further explored in the anti-apoptotic and pro-metastatic process., Results: We found that OPN-b is the dominant kind of OPN isoform in GC cell lines. Although the expression levels of three variants were all elevated in GC tissues, increased OPN-b or OPN-c expression could correlate with clinicopathological features. Functional analyses further showed that OPN-b most strongly promoted GC cell survival possibly by regulation of Bcl-2 family proteins and CD44v expressions. Moreover, OPN-c most effectively stimulated GC metastatic activity by increasing secretion of MMP-2, uPa, and IL-8., Conclusions: Our results suggest that OPN splice variants differentially exert clinicopathological features and biological functions in GC. Therefore, focusing on specific OPN isoform could be a novel direction for developing diagnostic and therapeutic approaches in GC.