B-type Raf kinase (BRAF) mutation is proved to be a critical predictive factor in papillary thyroid cancer (PTC) with aggressive characteristics. However, the association between BRAF mutation and cervical lymphatic metastasis in PTC is controversial.

The metabolic hormone leptin has been implicated in the pathogenesis of various malignancies and may contribute to the high rate of cancer in obese individuals. We reported that leptin and its receptor are expressed by melanoma tumors and cell lines, and that leptin stimulates proliferation of cultured melanoma cells. Here, we tested the hypothesis that leptin contributes to early melanoma progression by assessing its association with sentinel node positivity in cutaneous melanoma patients. The study enrolled 72 patients who were scheduled to undergo lymphatic mapping and sentinel node biopsy. Fasting blood was obtained before surgery, and serum leptin levels were measured by enzyme-linked immunosorbent assay (ELISA) with a "raw" (assay value) and an "adjusted" value (raw value divided by body mass index). Leptin levels and other clinicopathologic parameters were compared between sentinel node positive and negative groups. Logistic regression models were used to predict sentinel node status using leptin and other relevant clinical parameters. The raw and adjusted leptin levels were significantly higher in the 15 patients with positive sentinel nodes. These findings could not be attributed to differences in body mass indices. Univariate models revealed raw leptin, adjusted leptin, Breslow thickness, and mitotic rate as significant predictors of sentinel node status. Leptin levels and Breslow thickness remained significant in multivariate models. Survival and follow-up analysis revealed more aggressive disease in diabetic patients. Elevated serum leptin levels predict sentinel node metastasis in melanoma. Validation of this finding in larger cohorts should enable better stratification of early stage melanoma patients.

This study is firstly, to investigate the presence of microcalcification among the patients who underwent thyroid ultrasound and biopsy and to evaluate the incidence of intrathyroid lymphatic spread and cervical lymph node metastasis of thyroid cancer with thyroid microcalcifications. Also, we compared the diagnostic performance between fine needle aspiration (FNA) and core needle biopsy (CNB) for assessing parenchymal microcalcifications in the thyroid gland. We retrospectively assessed total 66 patients with thyroid microcalcifications on ultrasound. The histopathologic characteristics of the surgical specimens considered as the gold standard for diagnosing malignancy. Patients with surgically proven malignancy were evaluated for multifocality, intrathyroid lymphatic spread in the opposite lobe, or cervical lymph node metastasis. Among the 66 confirmed patients, 53 patients had malignant lesions (80.3%) and 13 patients had benign lesions (19.7%). The pathologic results of the 44 patients who underwent total thyroidectomy. Among them, 33 patients (75%) showed multifocality, 30 patients (68.2%) showed intrathyroid lymphatic tumor spread. CNB was performed on 41 patients, and FNA was performed on 54 patients. Both CNB and FNA were performed on 29 patients. There were no statistical differences in terms of diagnostic performance between CNB and FNA. Thyroid microcalcifications demonstrate a high prevalence of malignancy. Both CNB and FNA demonstrate similar diagnostic accuracies.

The present study was designed to investigate the expression of tumor-associated macrophages (TAMs) in gastric cancer and its clinicopathological relationship. In addition, we also aimed to analyze the relationship between helicobacter pylori (HP) infection and TAMs in gastric cancer.The protein expression of CD16 and CD163 in 90 gastric cancer tissues and 30 margin tissues was detected by immunohistochemistry. HP infection was detected in 90 gastric cancer tissues and 30 margin tissues by gram staining and immunohistochemistry.There was no clear correlation between CD16 macrophages and gastric cancer. The density of CD163 macrophages was not correlated with the general condition of tumor patients, but with tumor size, tumor differentiation, lymphatic metastasis, depth of invasion and TNM stage. Additionally, the infection rate of HP in gastric cancer tissues was significantly higher.In summary, TAMs are associated with tumor size, degree of differentiation, depth of invasion, lymph node metastasis and TNM stage, suggesting their critical role in the invasion and metastasis of gastric cancer.

To investigate the correlation between echinodermmicro tubule associated protein-like 4 (EML4)-anaplasticlymphomakinase (ALK), epidermal growth factor receptor (EGFR) and clinicopathological features in patients diagnosed with lung adenocarcinoma according to International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) international multidisciplinary classification of lung adenocarcinoma.Ninety patients diagnosed with lung adenocarcinoma underwent surgical pathological classification. Ventana immunohistochemical staining of the EML4-ALK was performed. The mutation of EGFR and EML4-ALK was detected by real-time polymerase chain reaction (RT-PCR) using the amplification refractory mutation system.The positive rate of EML4-ALK mutation was calculated as 6.7% (6/90), dominantly occurring in patients aged < 60 years. However, it was not correlated with the gender, smoking history, maximal tumor diameter, pleural invasion, lymphatic metastasis, or clinical staging. EML4-ALK fusion gene mutation was mainly associated with the predominant subtypes of acinar and solid tumors with mucin secretion. The mutation rate of EGFR was 60% (27/45). EGFR gene mutation mainly occurred in the female, those with no smoking history and tumor size < 3 cm, whereas it had no association with age, pleural invasion, lymphatic metastasis, or clinical staging. It was histologically characterized with micropapillary, lepidic, and papillary subtypes.The mutation rate of EML4-ALK is relatively high in lung adenocarcinoma patients aged<60 years, pathologically characterized with acinar and solid subtypes with mucin secretion. Female patients with no smoking habit, tumor size<3 cm, pathologically characterized with micropapillary, lepidic, and papillary subtypes had a high mutation rate of EGFR.

Published literatures have reported the relationship between hypoxic-inducible factor-2α (HIF-2α) expression and clinicopathological features in gastric cancer (GC), but the evaluated conclusions remain controversial. A meta-analysis was carried to examine the clinicopathological features and prognostic values of HIF-2α in patients with GC. Systematic detailed searches were performed to Pub Med, Cochrane Library, and EBSCO until to August 2015. Six studies (508 specimens) were included in this meta-analysis. HIF-2α-positive expression indicates an unfavorable prognosis value and advanced clinicopathological differences for the available patient dates with GC. Further multivariate meta-analysis revealed that HIF-2α-positive expression in gastric cancer associated with deeper tumor infiltration (OR = 3.08; 95%CI: 1.18-8.04), higher rates of lymphatic metastasis (OR = 3.26; 95%CI: 1.10-9.63), higher TNM stage (III+IV) (OR = 2.61; 95%CI: 1.40-4.84), and much lower 5-year overall survival (OR = 2.08; 95%CI: 1.21-3.58). Nevertheless, there is no association between HIF-2α-positive expression and worse tumor differentiation (OR = 2.03; 95%CI: 0.73-5.64). In addition, by this subgroup analysis, HIF-2α-positive expression associated with deeper tumor infiltration (OR = 3.81; 95%CI: 1.03-14.08), higher lymphatic metastasis (OR = 4.71; 95%CI: 1.08-20.50), higher TNM stage (OR = 3.21; 95%CI: 1.57-6.57), worse tumor differentiation (OR = 3.08; 95%CI: 1.51-6.31), and lower 5-year overall survival (OR = 2.34; 95%CI: 1.15-4.79). Our results indicate that HIF-2α overexpression can potently predict the poor prognosis and may be a potential therapeutic target for gastric carcinoma, according to the limited evidence. Meanwhile, further studies are needed to elucidate the accuracy of these results.

Recent studies have demonstrated that exon 19 deletion (19 Del) and exon 21 L858R mutation (L858R) are 2 different types of sensitive epidermal growth factor receptor (EGFR) mutations in nonsmall cell lung cancer (NSCLC). However, whether there are some differences between those 2 groups in baseline clinical characteristics is still unclear.We enrolled consecutive 1271 NSCLC patients detected with either 19 Del or L858R and collected their baseline clinical characteristics including age, sex, comorbidity, smoking and drinking status, body mass index (BMI), TNM stage, histologic type, differentiation, tumor maximum diameter (TMD), and CEA level. χ test and multivariate logistic regression analysis were used to compare the difference.We found a higher percentage of 19 Del in younger patients group (< = 50 yr) than L858R (P < 0.001) through χ test. Besides, patients with 19 Del have higher risk of lymph node metastasis (P < 0.001). However, there were no significant differences in other items of clinical characteristics between 19 Del and L858R. Multivariate analysis showed similar significant results. Subgroup analysis in different age groups (10 yr as an interval) and N stages (stratified by N0, N1, N2, and N3) also indicated above-mentioned trends.NSCLC patients with 19 Del are more likely to be young and have lymphatic metastasis than those with L858R. Age and N stage might be considered in predicting EGFR mutation type in NSCLC.

The aim of the study was to explore the association between mucin 5ac expression and cancer prognosis. A systematically comprehensive search was performed through PubMed, the Web of Science, and the China National Knowledge Infrastructure (CNKI). The prognostic value of mucin 5ac expression in cancer patients was evaluated. The overexpression of mucin 5ac was found to be significantly associated with a poor prognosis in cancer patients (pooled HR: 1.53, 95%CI: 1.158-2.028, P = 0.003). This association was also detected in a biliary subgroup (pooled HR: 1.83, 95%CI: 1.269-2.639, P = 0.001) and a gastrointestinal subgroup (pooled HR: 1.44, 95%CI: 1.069-1.949 P = 0.017). In the geography subgroup analysis, a statistical association was found in the Asian subgroup (pooled HR: 1.69, 95%CI: 1.200-2.384, P = 0.003). In the clinical characteristics analysis, a statistical association was found between the hyper expression of mucin 5ac and lymphatic metastasis. We indicated that mucin 5ac is a promising prognostic predictor for cancer, especially for biliary and gastrointestinal cancer, and is more suitable for predicting cancer prognoses in Asians.

The cell-surface glycoprotein, mesothelin, is normally present on mesothelial cells. Overexpression of mesothelin has been reported in many tumors and is correlated with poor outcome. We investigated the clinicopathologic significance of mesothelin expression in colorectal adenocarcinoma with microsatellites instability (MSI) status.Mesothelin expression was evaluated immunohistochemically in tissue microarray blocks from 390 colorectal adenocarcinoma samples. Mesothelin expression was interpreted according to the intensity and extent. A score of 2 was considered high expression. We analyzed the correlation between mesothelin expression and clinicopathologic characteristics.High mesothelin expression was observed in 177 (45.4%) out of 390 colorectal adenocarcinoma samples and was significantly associated with high histologic grade (P = .037), lymphatic invasion (P = .028), lymph node metastasis (P = .028), and high AJCC stage (P = .026). Kaplan-Meier survival curves revealed no significant difference between patients with high mesothelin expression and patients with low mesothelin expression in both recurrence-free survival (RFS) and cancer-specific survival (P = .609 and P = .167, respectively). In subgroup survival analyses, high mesothelin expression was associated with poor RFS in the MSI-High group of colorectal adenocarcinoma (P = .004).High mesothelin expression was significantly associated with aggressive phenotypes and poor patient outcome in MSI-High colorectal adenocarcinoma.

An overexpression of S-phase kinase-associated protein 2 (SKP2) is frequently observed in human cancer progression and metastasis, and evidence suggests that SKP2 plays a proto-oncogenic role both in vitro and in vivo. However, the function of SKP2 in gastric adenocarcinoma remains largely obscure. We investigated SKP2 expression in human gastric carcinomas.Tissue samples were acquired from 182 cases of gastric adenocarcinoma that were surgically resected from 2006 to 2012. Immunohistochemical staining for SKP2, Beclin-1, and forkhead box protein P3 (FOXP3) was performed. Pearson chi-square test was used to evaluate the associations among clinicopathological variables. The Kaplan-Meier method, the log-rank test, and the Cox proportional-hazards model were used in the analysis of the overall survival (OS) and disease-free survival (DFS).As a result, SKP2 overexpression in gastric adenocarcinomas showed a significant correlation with several favorable clinical factors, including the tumor size, T category, N category, lymphatic invasion, vascular invasion, OS, and DFS. SKP2 expression was positively correlated with the tumoral FOXP3, Beclin-1 expression, and regulatory T cell (Treg) infiltration. The difference in DFS between the SKP2 positive and negative group was attenuated by FOXP3 high expression, Beclin-1 high expression, and Tregs infiltration. Attenuation of the difference in OS by FOXP3 high expression, Beclin-1 high expression, and Tregs infiltration was not significant. In multivariable analysis, SKP2 expression was not correlated with OS and DFS.Our study showed a complex interrelationship between SKP2 and Beclin-1 and FOXP3 expression in gastric adenocarcinoma. The antioncogenic effect of Beclin-1 and FOXP3 expression in gastric adenocarcinoma is related to SKP2 expression.

Lymph node metastasis plays a crucial role in predicting prognosis in advanced gastric cancer (AGC). In the present study, we formulated a fibrosis ratio (FR), defined as the number of metastatic lymph nodes with fibrosis divided by the total number of lymph nodes, and sought to determine whether it can be used to predict the prognosis of patients with AGC and improve on existing node staging. We retrospectively analyzed 161 patients who underwent curative resection for node-positive AGC between 2001 and 2010, evaluating the association between FR, lymph node ratio (LNR), and micrometastasis, and the relationship between FR and clinicopathologic findings, overall survival (OS) and disease-free survival (DFS). A high FR was significantly related to T stage (P < .001), N stage (P < .001), tumor stage (P < .001), lymphatic invasion (P < .001), and venous invasion (P = .007). FR was significantly correlated with an increased number of metastatic lymph nodes (P = .001, R = 0.869) and LNR (P = .001, R = 0.943), but not with total harvested lymph nodes. Patients with micrometastases had a lower FR, compared with those without micrometastases (P < .001). A survival analysis showed poor OS for patients in the entire cohort (P < .001); N1 (P = .002), N2 (P = .004), N3a (P = .010), and N3b (P = .003) stages; and groups with high LNR (P = .013) and low LNR (P = .001). DFS was also poor for the entire cohort (P < .001) and the N2 (P = .013), N3b (P = .002), high-LNR (P = .036), and low-LNR (P = .001) groups, but not the N1 or N3a group. Univariate and multivariate analyses revealed that high FR was an independent prognostic factor for OS (hazard ratio [HR], 2.780; CI, 1.655-4.670; P < .001) and DFS (HR, 2.051; CI, 1.199-3.508; P = .009) in AGC. Collectively, our findings indicate that high FR is associated with adverse clinicopathologic parameters in AGC, clearly establishing nodal fibrosis as a pathological finding with value in predicting poor prognosis of patients with AGC. Thus, combining current N stage and LNR diagnostics with FR could improve prognostic prediction in AGC.