A novel PDX modeling strategy and its application in metabolomics study for malignant pleural mesothelioma.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare and aggressive carcinoma located in pleural cavity. Due to lack of effective diagnostic biomarkers and therapeutic targets in MPM, the prognosis is extremely poor. Because of difficulties in sample extraction, and the high rate of misdiagnosis, MPM is rarely studied. Therefore, novel modeling methodology is crucially needed to facilitate MPM research. METHODS: A novel patient-derived xenograft (PDX) modeling strategy was designed, which included preliminary screening of patients with pleural thickening using computerized tomography (CT) scan, further reviewing history of disease and imaging by a senior sonographer as well as histopathological analysis by a senior pathologist, and PDX model construction using ultrasound-guided pleural biopsy from MPM patients. Gas chromatography-mass spectrometry-based metabolomics was further utilized for investigating circulating metabolic features of the PDX models. Univariate and multivariate analysis, and pathway analysis were performed to explore the differential metabolites, enriched metabolism pathways and potential metabolic targets. RESULTS: After screening using our strategy, 5 out of 116 patients were confirmed to be MPM, and their specimens were used for modeling. Two PDX models were established successfully. Metabolomics analysis revealed significant metabolic shifts in PDX models, such as dysregulations in amino acid metabolism, TCA cycle and glycolysis, and nucleotide metabolism. CONCLUSIONS: To sum up, we suggested a novel modeling strategy that may facilitate specimen availability for MM research, and by applying metabolomics in this model, several metabolic features were identified, whereas future studies with large sample size are needed.

In situ hybridization: Introduction to techniques, applications and pitfalls in the performance and interpretation of assays.

In situ hybridization (ISH) has become a common laboratory technique used for the analysis of gene expression and for the localization of specific DNA and RNA molecules in cells. Many different methods of performing ISH have been described. These techniques have evolved into important tools in basic scientific research and in clinical diagnoses. One of the goals of ISH is to localize gene sequences in situ and to visualize the products within cells while preserving cell integrity. This allows for meaningful anatomical and histological interpretation of the localized product(s) within heterogeneous tissues. Because of the possibility of false positive and false negative results that may occur with ISH assays, familiarity with the pathophysiology of the molecules that are analyzed and the cellular processes involved as well as with limitations of the assays can help to avoid erroneous diagnoses with clinical specimens.

Loss of PIM1 correlates with progression and prognosis of salivary adenoid cystic carcinoma (SACC).

BACKGROUND: Increasing evidence indicates that PIM1 is a potential prognostic marker and target for cancer treatment but its precise mechanisms of action remain to be determined in salivary adenoid cystic carcinoma (SACC). This study aims to decipher the prognostic and mechanistic role of PIM1 in progression of SACC cells and tumor tissues. METHODS: A SACC cell line (ACC-M) was transfected with shRNA plasmids targeting the PIM1 gene. The expression levels of PIM1, RUNX3 and p21 were measured by quantitative real-time PCR and western blot. Subcellular translocalization of RUNX3 and p21 proteins was assessed using immunofluorescence, and cell cycle phase was quantified using flow cytometry. A total of 97 SACC patients were retrospectively analyzed by clinicopathologic characteristics and survival outcomes. RESULTS: After down-regulation of PIM1 in ACC-M cells, RUNX3 and p21 proteins were translocated from cytoplasm to nucleus, with a decrease of p21 expression and increase of G0/G1 phase cells. PIM1 and RUNX3 levels show a distinct covariance. PIM1 is associated with T-status, lymph node involvement, nerve invasion, and distant metastasis in SACC tissues. Patients with low PIM1 level had a better outcome than those with higher PIM1 level. CONCLUSIONS: PIM1 is multifunctional in ACC-M cells and it serves as a neoteric therapeutic target and potential prognostic marker for SACC patients.

Recent Advances in the Classification of Low-grade Papillary-like Thyroid Neoplasms and Aggressive Papillary Thyroid Carcinomas: Evolution of Diagnostic Criteria.

Papillary thyroid carcinomas account for ∼80% of well-differentiated thyroid tumors. During the past decade, several new variants of papillary-like thyroid neoplasms and papillary thyroid carcinomas have been recognized. Some of these neoplasms that were previously classified as malignant have been reclassified as low-grade neoplasms, as the diagnostic criteria have evolved. Similarly, some of the papillary thyroid carcinomas that were previously classified as conventional or classic papillary thyroid carcinomas have now been recognized as more aggressive variants of papillary thyroid carcinomas. Recognizing these differences becomes more important for the proper medical, surgical, and radiotherapeutic management of patients with these neoplasms.

The evolving concept of cancer stem-like cells in thyroid cancer and other solid tumors.

The cancer stem-like cell (CSC) hypothesis postulates that a small population of cells in a cancer has self-renewal and clonal tumor initiation properties. These cells are responsible for tumor initiation, growth, recurrence and for resistance to chemotherapy and radiation therapy. CSCs can be characterized using markers such as SSEA-1, SSEA-4, CD44, CD24, ALDEFLUOR and others. CSCs form spheres when they are cultured in serum-free condition in low attachment plates and can generate tumors when injected into immune-deficient mice. During epithelial to mesenchymal transition (EMT), cells lose cellular adhesion and polarity and acquire an invasive phenotype. Recent studies have established a relationship between EMT and increased numbers of CSCs in some solid malignancies. Non-coding RNAs such as microRNAs and long non-coding RNAs (lncRNAs) have been shown to have important roles during EMT and some of these molecules also have regulatory roles in the proliferation of CSCs. Specific lncRNAs enhanced cell migration and invasion in breast carcinomas, which was associated with the generation of stem cell properties. The tumor microenvironment of CSCs also has an important role in tumor progression. Recent studies have shown that the interaction between tumor cells and the local microenvironment at the metastatic site leads to the development of premetastatic niche(s) and allows for the proliferation of the metastatic cells during colonization. The role of exosomes in the microenvironment during the EMT program is currently a major area of research. This review examines CSCs and the relationship between EMT and CSCs in solid tumors with emphasis on thyroid CSCs. The role of non-coding RNAs and of the microenvironment in EMT and in tumor progression are also examined. This review also highlights the growing number of studies that show the close association of EMT and CSCs and the role of exosomes and other elements of the tissue microenvironment in CSC metastasis. A better understanding of these mechanisms will lead to more effective targeting of primary and metastatic malignancies.

The roles of the epithelial-mesenchymal transition marker PRRX1 and miR-146b-5p in papillary thyroid carcinoma progression.

Thyroid carcinoma is the most common endocrine malignancy, and papillary thyroid carcinoma represents the most common thyroid cancer. Papillary thyroid carcinomas that invade locally or metastasize are associated with a poor prognosis. We found that, during epithelial-mesenchymal transition (EMT) induced by transforming growth factor-ß1 (TGF-ß1), papillary thyroid carcinoma cells acquired increased cancer stem cell-like features and the transcription factor paired-related homeobox protein 1 (PRRX1; alias PRX-1), a newly identified EMT inducer, was markedly up-regulated. miR-146b-5p was also transiently up-regulated during EMT, and in siRNA experiments miR-146b-5p had an inhibitory role on cell proliferation and invasion during TGF-ß1-induced EMT. We conclude that papillary thyroid carcinoma tumor cells exhibit increased cancer stem cell-like features during TGF-ß1-induced EMT, that miR-146b-5p has a role in cell proliferation and invasion, and that PRRX1 plays an important role in papillary thyroid carcinoma EMT and disease progression.

Pheochromocytomas and Paragangliomas: An Update on Recent Molecular Genetic Advances and Criteria for Malignancy.

Pheochromocytomas are uncommon neuroendocrine tumors arising in the adrenal medulla, whereas paragangliomas arise from chromaffin cells in sympathetic and parasympathetic locations outside of the adrenal gland. Molecular genetic studies in the past few years have identified >10 genes involved in the pathogenesis of pheochromocytomas and paragangliomas, including RET oncogene, involved in the pathogenesis of multiple endocrine neoplasia (MEN) 2A and 2B, von Hippel-Lindau tumor-suppressor gene, neurofibromatosis type 1 gene, succinate dehydrogenase, THEM127, and several others. The presence of genetic alterations in some of these genes such as in MEN 2A and 2B can be used to diagnose these disorders clinically, and other mutations such as succinate dehydrogenase can be used in the pathologic prediction of benign and malignant pheochromocytomas and paragangliomas. Although it has been difficult to separate benign and malignant pheochromocytomas and paragangliomas, recent studies that may predict the behavior of these chromaffin-derived neoplasms have been reported. The Pheochromocytoma of the Adrenal Scale Score and the Grading system for Adrenal Pheochromocytoma and Paraganglioma scoring system are also discussed.

Primary Squamous Cell Carcinoma of the Thyroid Has a Molecular Genetic Profile Distinct From That of Anaplastic Thyroid Carcinoma: A Whole Exome Sequencing and Gene Expression Profiling Study.

BACKGROUND: Primary squamous cell carcinoma (SCC) of the thyroid and anaplastic thyroid carcinoma (ATC) show significant clinical and histologic overlap. Their biological behaviors are so similar that the fifth WHO updates SCC as a morphologic pattern of ATC rather than a separate entity. However, molecular genomic evidence that determines them as the same histologic type is limited. We aimed to explore whether they belong to the same classification from a molecular-typing perspective. METHODS: A cohort enrolled 15 SCCs and 15 ATCs was collected. Whole exome sequencing (WES) and RNA-sequencing were performed to analyze molecular genetic and gene-expression profiles. RESULTS: Significantly differential-mutant genes were BRAF, DPCR1, PCYOX1L, BRSK2, NRG1, PRR14L, TET1, VAMP4 suggesting differences in mutation level, as well as differences in high-frequency mutated genes, and SCC had a much lower tumor mutation burden than ATC. Mutational co-occurrence and mutual exclusion were less frequent in SCC than in ATC. 2047 differential-express genes were screened, indicating differences in gene expression were extremely strong. In principal component analysis, ATC and SCC could be notably clustered together, respectively, meanwhile they could be explicitly distinguished. Unsupervised clustering analysis validated they can indeed be clearly separated from each other which demonstrated that they may be two distinctive entities. CONCLUSIONS: It is controversial yet SCC is classified as a morphologic pattern of ATC. We revealed that SCC exhibited molecular genetic characteristics distinct from ATC. Although the fifth WHO categorizes them together, this study may provide strong molecular genetic evidence for the next edition of WHO classification that may allow for the separation of thyroid SCC from ATC.

Total thyroidectomy vs bilateral subtotal thyroidectomy in patients with Graves' diseases: a meta-analysis of randomized clinical trials.

BACKGROUND: Conducting total thyroidectomy (TT) or subtotal thyroidectomy (ST) in patients with Graves' disease remains controversial. We performed a meta-analysis based on the published randomized controlled trials to evaluate the complications of TT vs ST. METHODS: We searched multiple electronic databases for prospective, randomized, controlled trials related to safety and effectiveness of TT vs ST. Relative risk (RR) was estimated with 95% confidence interval (CI) based on an intention-to-treat analysis. We considered the following outcomes: recurrent hyperthyroidism, ophthalmopathy progression, temporary and permanent hypoparathyroidism, temporary and permanent recurrent laryngeal nerve palsy (RLNP) and post-operative bleeding. RESULTS: Four trials with 674 patients (342 with TT, 332 with ST) were analysed. Although the overall rates of ophthalmopathy progression were similar between TT and ST (RR 0·92, 95% CI = 0·50-1·71; P = 0·80), TT was associated with a significant reduction in recurrent hyperthyroidism (RR 0·14, 95% CI = 0·05-0·41; P < 0·01). The pooled RR of post-operative bleeding for TT was similar to that for ST (RR 0·32, 95% CI = 0·05-1·96; P = 0·22). However, comparing with ST, the RR of temporary hypoparathyroidism was significantly higher for TT (RR 2·66, 95% CI = 1·89-3·73; P < 0·01). There was no significant difference in permanent hypoparathyroidism (RR 2·30, 95% CI = 0·78-6·76; P = 0·13), temporary (RR 1·08, 95% CI = 0·47-2·48; P = 0·85) and permanent RLNP (RR 1·54, 95% CI = 0·41-5·73; P = 0·52) between the two groups. CONCLUSIONS: With regard to ophthalmopathy progression, post-operative bleeding, permanent hypoparathyroidism, temporary and permanent RLNP, TT is consistent with ST in patients with Graves' disease. However, TT is associated with a reduced incidence of recurrent hyperthyroidism and results in an increase in temporary hypoparathyroidism. Therefore, TT should be proposed for the treatment of Graves' disease.

Preoperative versus intraoperative endoscopic sphincterotomy in patients with gallbladder and suspected common bile duct stones: system review and meta-analysis.

BACKGROUND: Conducting preoperative versus intraoperative endoscopic sphincterotomy in patients with gallbladder and suspected common bile duct stones remains controversial. We conducted a meta-analysis to evaluate the outcomes of preoperative endoscopic sphincterotomy (POES) versus intraoperative endoscopic sphincterotomy (IOES). METHODS: We searched multiple electronic databases for prospective, randomized, controlled trials related to safety and effectiveness of POES versus IOES. Relative risk ratios (RRs) were estimated with 95 % confidence intervals (CI) based on an intention-to-treat analysis. We considered the following outcomes: clearance rate, postprocedural complications, and hospital stay. RESULTS: Five trials with 631 patients (318 with POES, 313 with IOES) were analyzed. Although the overall rates of common bile duct stone clearance were similar between POES and IOES (RR 0.96, 95 % CI 0.91-1.01; p = 0.13), the failure rate of common bile duct cannulation during endoscopic retrograde cholangiopancreatography (ERCP) was significantly higher for IOES (RR 2.54, 95 % CI 1.23-5.26; p = 0.01). The pooled RR after POES for overall complication rates was similar to that for IOES (RR 1.56, 95 % CI 0.94-2.59; p = 0.09). However, compared with IOES, the RR risk of ERCP-related complications was significantly higher for POES (RR 2.27, 95 % CI 1.18-4.40, p = 0.01), especially in the patients at high risk of developing post-ERCP pancreatitis. There was no significant difference in morbidity after laparoscopic cholecystectomy or required subsequent open surgery between the two groups. In the subgroup analyses, the RR risks of post-ERCP pancreatitis were significantly higher for POES (RR 4.85, 95 % CI 1.41-16.66, p = 0.01), and mean hospital stay was longer in the POES group (RR 2.22, 95 % CI 1.98-246; p < 0.01). However, the rates of bleeding, perforation, cholangitis, cholecystitis, and gastric ulceration did not differ significantly between POES and IOES. CONCLUSIONS: With regard to the stone clearance and overall complication rates, POES is equal to IOES in patients with gallbladder and common bile duct stones. However, IOES is associated with a reduced incidence of ERCP-related pancreatitis and results in a shorter hospital stay.

Updated systematic review and meta-analysis of randomized clinical trials comparing carotid artery stenting and carotid endarterectomy in the treatment of carotid stenosis.

BACKGROUND: To compare carotid artery stenting (CAS) versus carotid endarterectomy (CEA) in the treatment of carotid stenosis, including two recently published, large, prospective, randomized trials of these therapies. METHODS: We searched electronic databases for prospective, randomized, controlled trials involving carotid stenosis patients who underwent CAS or CEA, focusing on studies published in 1995 to 2010. Primary outcomes were death, stroke, and myocardial infarction. RESULTS: Thirteen trials containing 7,501 patients were analyzed, and odds ratios (ORs) were calculated for CAS versus CEA. The risk of stroke or death within 30 days was higher after CAS than CEA (OR = 1.57; 95% confidence interval [CI] = 1.11-2.22), especially in previously symptomatic patients (OR = 1.89; 95% CI = 1.48-2.41). However, the risk of stroke or death within 1 year was comparable (OR = 1.12; 95% CI = 0.55-2.30). In a subgroup analysis, the risk of death and disabling stroke at 30 days did not differ significantly between CEA and CAS (death: OR = 1.43; 95% CI = 0.85-2.40; disabling stroke: OR = 1.28; 95% CI = 0.89-1.83), whereas the rate of nondisabling stroke within 30 days was much higher in the CAS group (OR = 1.87; 95% CI = 1.40-2.50). The risks of myocardial infarction within 30 days and 1 year were significantly less for CAS. CONCLUSION: CAS is inferior to CEA with regard to the incidence of stroke or death for periprocedural outcomes, especially in symptomatic patients. However, CAS was associated with a lower incidence of myocardial infarction. These procedures may be considered complementary rather than competing modes of therapy, each of which can be optimized with careful patient selection.

Metabolomics of a cell line-derived xenograft model reveals circulating metabolic signatures for malignant mesothelioma.

BACKGROUND: Malignant mesothelioma (MM) is a rare and highly aggressive cancer. Despite advances in multidisciplinary treatments for cancer, the prognosis for MM remains poor with no effective diagnostic biomarkers currently available. The aim of this study was to identify plasma metabolic biomarkers for better MM diagnosis and prognosis by use of a MM cell line-derived xenograft (CDX) model. METHODS: The MM CDX model was confirmed by hematoxylin and eosin staining and immunohistochemistry. Twenty female nude mice were randomly divided into two groups, 10 for the MM CDX model and 10 controls. Plasma samples were collected two weeks after tumor cell implantation. Gas chromatography-mass spectrometry analysis was conducted. Both univariate and multivariate statistics were used to select potential metabolic biomarkers. Hierarchical clustering analysis, metabolic pathway analysis, and receiver operating characteristic (ROC) analysis were performed. Additionally, bioinformatics analysis was used to investigate differential genes between tumor and normal tissues, and survival-associated genes. RESULTS: The MM CDX model was successfully established. With VIP > 1.0 and P-value < 0.05, a total of 23 differential metabolites were annotated, in which isoleucine, 5-dihydrocortisol, and indole-3-acetamide had the highest diagnostic values based on ROC analysis. These were mainly enriched in pathways for starch and sucrose metabolism, pentose and glucuronate interconversions, galactose metabolism, steroid hormone biosynthesis, as well as phenylalanine, tyrosine and tryptophan biosynthesis. Further, down-regulation was observed for amino acids, especially isoleucine, which is consistent with up-regulation of amino acid transporter genes SLC7A5 and SLC1A3 in MM. Overall survival was also negatively associated with SLC1A5, SLC7A5, and SLC1A3. CONCLUSION: We found several altered plasma metabolites in the MM CDX model. The importance of specific metabolic pathways, for example amino acid metabolism, is herein highlighted, although further investigation is warranted.

Aurora Kinase A as a Diagnostic and Prognostic Marker of Malignant Mesothelioma.

BACKGROUND: Malignant mesothelioma (MM) is a highly aggressive cancer with a poor prognosis. Despite the use of several well-known markers, the diagnosis of MM is still challenging in some cases. we applied bioinformatics to identify key genes and screen for diagnostic and prognostic markers of MM. METHODS: The expression profiles of GSE2549 and GSE112154 microarray datasets from the Gene Expression Omnibus database contained 87 cases of MM tissue and 8 cases of normal mesothelial tissue in total. The GEO2R tool was used to detect differentially expressed genes (DEGs). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of DEGs were performed using DAVID Bioinformatics Resources. The DEGs protein-protein interaction networks were constructed from the STRING database. Cytoscape was used to identify significant modules and hub genes. The GEPIA database was used to explore relationships between hub genes and prognosis of MM. Immunohistochemistry was used to analyze protein expression in tissue microarrays with 47 Chinese MM tissues. Statistical analyses diagnostic and prognostic values. RESULTS: 346 DEGs were identified: 111 genes upregulated, and 235 downregulated. GO analysis showed that the primary biological processes of these DEGs were cell adhesion, leukocyte migration, and angiogenesis. The main cellular components included the extracellular space, extracellular exosome, and extracellular region. The molecular functions were integrin binding, heparin binding, and calcium ion binding. KEGG pathway analysis showed that DEGs are primarily involved in PPAR signaling pathway, extracellular matrix-receptor interactions, and regulation of lipolysis in adipocytes. Survival analysis showed that seven genes-AURKA, GAPDH, TOP2A, PPARG, SCD, FABP4, and CEBPA-may be potential prognostic markers for MM. Immunohistochemical studies showed that Aurora kinase A (AURKA gene encode, Aurora-A) and GAPDH were highly expressed in MM tissue in comparison with normal mesothelial tissue. Kaplan-Meier analysis confirmed a correlation between Aurora-A protein expression and overall survival but did not confirm a correlation with GAPDH. The receiver operating characteristic curves of Aurora-A protein expression suggested acceptable accuracy (AUC = 0.827; 95% CI [0.6686 to 0.9535]; p = 0.04). The sensitivity and specificity of Aurora-A were 83.33% and 77.78%, respectively. CONCLUSION: Aurora-A could be an optimal diagnostic biomarker and a potential prognostic marker for MM.

Impact of Hepatic Steatosis on the Antiviral Effects of PEG-IFNα-2a in Patients with Chronic Hepatitis B and the Associated Mechanism.

OBJECTIVE: To investigate the risk factors for hepatic steatosis in chronic hepatitis B (CHB), to determine its correlation with liver necroinflammation and fibrosis and response to peginterferon alpha-2a (PEG-IFNα-2a) antiviral therapy, and to explore the mechanisms underlying the poor antiviral effect of PEG-IFNα-2a in CHB patients with hepatic steatosis. METHODS: We analysed the impact of hepatic steatosis on the antiviral effect of PEG-IFNα-2a on CHB patients in a cohort of 226 patients who underwent pretherapeutic liver biopsy. To assess the complete response (CR), virological response (VR), and biochemical response (BR), the 226 patients were treated with PEG-IFNα-2a for 48 weeks and were followed-up for 24 weeks. The expressions of hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) in the liver tissue were detected in all patients to explore the possible mechanism of hepatic steatosis with regard to antiviral effects. RESULTS: The patients were divided into four groups based on the severity of hepatic steatosis: 119 with no steatosis, 76 with mild steatosis, 22 with moderate steatosis, and 9 with severe steatosis. In the hepatic steatosis groups, the proportions of male patients, patients aged >40 years, patients with hyperuricaemia, patients with a BMI > 23 kg/m2, and total cholesterol (TC), triglyceride (TG), glucose (GLU), and uric acid (UA) levels were significantly higher than those in the group without steatosis, whereas the alanine aminotransferase (ALT) and aspartate transaminase (AST) levels were significantly lower than those in the group without steatosis. The multivariate analysis results indicated that a BMI > 23 kg/m2 was independently associated with CHB patients with hepatic steatosis; the levels of baseline AST and UA were independently associated with CHB patients with significant hepatic steatosis, and the baseline AST level was independently associated with significant liver fibrosis. After 48 weeks of treatment and 24 weeks of follow-up, the rates of CR, VR, and BR had gradually decreased, whereas the severity of hepatic steatosis had increased. CONCLUSION: Hepatic steatosis can reduce the efficacy of PEG-IFNα-2a in the treatment of CHB patients, and its mechanism may be related to the different HBcAg expression patterns in liver tissue.

Identification and validation of circulating exosomes-based liquid biopsy for esophageal cancer.

BACKGROUND: Early detection of esophageal squamous cell carcinoma (ESCC) recurrence is a key element for follow-up care and surveillance. The aim of this study is to detect the level of circulating exosomes (CEs) in ESCC patient and clarify its clinical significance. METHODS: In this study, 200 serum samples of ESCC patients were obtained from the Zhejiang Cancer Hospital Biospecimen Repository. Total CEs were purified by selectively capturing epithelial cell adhesion molecule positive exosomes, using magnetic-bead technique. enzyme-linked immunosorbent assay (ELISA) was performed to measure the concentration level of CEs. The oncogenic potential of CEs was analyzed in vitro. RESULTS: Serum concentration of CEs was significantly higher in ESCC patients than in healthy controls (P < 0.01). Receiver-operating characteristic curve analysis demonstrated that CEs concentration could distinguish patients with ESCC from healthy individuals with a sensitivity of 75% and a specificity of 85%. Kaplan-Meier analysis demonstrated that the increased CEs concentration was associated with poor overall survival (P = 0.01) and progression free survival (P = 0.03) in ESCC patients. Multivariate cox regression analysis revealed that CEs concentration was an independent prognostic marker for overall survival in ESCC patients (P < 0.01). Results from transwell and wound scratching experiments showed that the CEs could promote cell migration and invasion. CONCLUSIONS: This study clearly demonstrates that CEs from ESCC patients are stable enough to be measured and their levels in ESCC patients are significantly upregulated. Circulating exosomes could serve as a novel noninvasive biomarker for detection of ESCC. Their involvement in carcinogenesis must be further established.

Clinicopathological and Prognostic Significance of WW Domain Binding Protein 5 Expression in Papillary Thyroid Carcinoma.

OBJECTIVES: Many patients with papillary thyroid cancer (PTC) have a high recurrence risk and poor prognosis, and the main obstacle to the clinical diagnosis and treatment of PTC is lack of effective predictive molecular markers. The purpose of this study was to investigate the clinicopathological and prognostic implications of WW domain binding protein 5 (WBP5) expression in PTC. MATERIALS AND METHODS: Immunohistochemistry of WBP5 was performed using tissue microarrays of 131 patients with PTC who underwent surgery during January 2006 and January 2010 in the Zhejiang Cancer Hospital. Statistical analyses were conducted to evaluate the association between WBP5 expression and the clinicopathological features and to analyze the disease-free survival (DFS) and prognostic factors. RESULTS AND CONCLUSION: The positive expression rate of WBP5 in PTC and the adjacent normal tissues was 42.75% (56/131) and 45.45% (10/22), respectively. WBP5 expression was significantly correlated with bilaterality, capsule invasion, and N-stage, and it was a favorable factor of DFS. Moreover, patients with a high WBP5 expression exhibited reduced risk of disease recurrence compared with that in patients with low WBP5 expression in the univariate analysis, whereas the multivariate analysis suggested that WBP5 was not an independent prognostic factor. Our results indicate that WBP5 might be a favorable prognosis indicator of PTC.

Breast cancer metastasis to thyroid: a retrospective analysis.

BACKGROUND: Breast cancers metastasizing to thyroid gland are relatively uncommon in clinical practice. OBJECTIVE: Retrospective analysis of data from breast cancer patients with thyroid metastasis (TM). METHODS: The US suspected, fine-needle aspiration cytology (FNAC) confirmed TM in breast cancer patients, treated between 2005 and 2015 at our hospital, was retrospectively analyzed. The data were re-evaluated by the pathologist and radiologist who were blinded to the patients' data. RESULTS: FNAC and immunohistochemistry confirmed the ultrasonography (US) suspected TM in eight breast cancer patients. Clinically both unilateral and bilateral TM was seen, which were symptomless and metachronously (6-121 months) metastasized. Six of eight cases exhibited recurrence/distant metastasis and were treated with chemotherapy/thyroidectomy of which two cases passed away. The remaining two patients had no recurrences/distant metastases and were treated with partial/total thyroidectomy. Post-chemotherapy US showed more homogenous thyroid parenchyma with gathering of calcification that reduced in size, revealing the sensitiveness of TM to chemotherapy. CONCLUSION: US was useful in screening TM in breast cancer patients. Both partial and total thyroidectomy was effective in disease free survival of isolated TM cases, with controlled primary condition. TM responded well to chemotherapy in most of the recurrent breast cancer cases with or without distant metastasis.

Improving the Accuracy of Mesothelioma Diagnosis in China.

INTRODUCTION: In the Western world, malignant mesothelioma (MM) is most prevalent in the pleura of older males who have been professionally exposed to asbestos. Information about MM from rapidly industrializing countries such as China is minimal. There is concern that a proportion of MM diagnoses in China may be incorrect because most Chinese physicians do not have experience diagnosing this rare cancer. We recently reported an unusually high incidence of peritoneal MM among eastern Chinese female patients. Here, we review the accuracy of MM diagnoses in China and provide suggestions to improve the accuracy of diagnosis. METHODS: We reviewed 92 pathological diagnosis of MM in 2002-2015 from two reference centers in the province of Zhejiang in eastern China. We performed a large set of immunohistochemistry analyses to increase the reliability of the diagnosis. RESULTS: We confirmed the MM diagnosis in 12 of 34 of the pleural tumors (35.3%), in 38 of 56 of the peritoneal tumors (67.9%), and in two of two of the MMs of the tunica vaginalis (100%). MMs were characterized by tumor cells showing nuclear Wilms tumor 1 and calretinin staining and by strong membranous staining for cytokeratin CAM5.2. The results of staining for the epithelial markers carcinoembryonic antigen, thyroid transcription factor-1, MOC31, BerEP4, p63, p40, paired box 8, ER and PR were negative. BRCA1 associated protein 1 nuclear staining was lost in percentages similar to what has been reported for samples from Western countries. CONCLUSIONS: Our findings suggest that MM-especially in its pleural localization-is often misdiagnosed in eastern China. Identifying pitfalls and possible solutions in the pathological diagnosis of MM will affect both the standard of care and research in China.