Association between Pax8-PPARandgamma;1 Rearrangement and Follicular Thyroid Cancer: a Meta-Analysis.

BACKGROUND: Pax8 and peroxisome proliferator-activated receptor gamma 1 gene (Pax8-PPARγ1) are important factors in tumors. Several studies have suggested that follicular thyroid cancer may arise from Pax8- PPArγ1 rearrangement. In order to have a better understanding of the association between Pax8-PPARγ1 rearrangement and follicular thyroid cancer, we conducted the presenmt meta-analysis. MATERIALS AND METHODS: The information was extracted from PubMed, EMBASE and Web of Science. Statistic analysis was performed with Stata12.0 software. Odds ratios (ORs) were calculated using a fixed-effects model. We also performed heterogeneity and publication bias analyses. RESULTS: Nine studies including 198 follicular thyroid cancer patients and 268 controls were considered eligible. The frequency of Pax8-PPARγ1 rearrangement was significantly higher in the follicular thyroid cancer group than in the control group, with a pooled OR of 6.63 (95%CI=3.50-12.7). In addition, through subgroup analysis, the OR between Pax8-PPARγ1 rearrangement and follicular thyroid cancer was 6.04 (95%CI = 3.18-11.5) when using benign tumor tissues as controls. The OR for the method subgroup was 9.99 (95% CI =4.86-20.5) in the RT-PCR. CONCLUSIONS: The final results demonstrated that Pax8-PPARγ1 rearrangement has significant association with follicular thyroid cancer.

Cancer Research Advance in CKLF-like MARVEL Transmembrane Domain Containing Member Family (Review).

CKLF-like MARVEL transmembrane domain-containing family (CMTM) is a novel family of genes first reported at international level by Peking University Human Disease Gene Research Center. The gene products are between chemokines and the transmembrane-4 superfamily. Loaceted in several human chromosomes, CMTMs, which are unregulated in kinds of tumors, are potential tumor suppressor genes consisting of CKLF and CMTM1 to CMTM8. CMTMs play important roles in immune, male reproductive and hematopoietic systems. Also, it has been approved that CMTM family has strong connection with diseases of autoimmunity, haematopoietic system and haematopoietic system. The in-depth study in recent years found the close relation between CMTMs and umorigenesis, tumor development and metastasis. CMTM family has a significant clinical value in diagnosis and treatment to the diseases linking to tumor and immune system.

Different expression pattern and significance of p14ARF-Mdm2-p53 pathway and Bmi-1 exist between gastric cardia and distal gastric adenocarcinoma.

Recent studies have suggested that adenocarcinoma of gastric cardia (GCA) is distinct from distal stomach, with different risk factors, tumor characteristics, and biological behavior. The aim of this study is to evaluate the possible difference in the expressions of p14ARF, Mdm2, p53, and Bmi-1 by immunohistochemical staining on paraffin-embedded tissues of gastric cardia adenocarcinoma (GCA; n = 74) and distal gastric adenocarcinoma (DGA; n = 41). The results showed that the percentage of p14ARF-negative expression, Mdm2 overexpression, p53-positive expression, and p53 pathway abnormality (p14ARF(-)/Mdm2(+)/p53(+)) were all significantly higher in GCA than those in DGA (P < .05). Further analysis showed that in GCA, the negative expression of p14ARF was significantly associated with poor differentiation, Mdm2 overexpression with tumor stage and lymph node metastasis, and positive p53 expression with tumor stage (P < .05), whereas in DGA, only Mdm2 overexpression was related with well/moderate differentiation (P < .05). Abnormality of the p53 pathway was significantly correlated with poorer differentiation only in GCA (P < .05). The positive expression of Bmi-1 in all cases of GCA and DGA was significantly higher than normal gastric mucosa epithelium, but no difference was found between GCA and DGA (P > .05). Thus, the results in this study confirmed that different expression pattern and clinicopathologic significance of the p14ARF-Mdm2-p53 pathway did exist between GCA and DGA. The results further support the hypothesis that different mechanisms may be involved in the development and progression of adenocarcinoma from cardia and distal portion of stomach.

Differences of immunophenotypic markers and signaling molecules between adenocarcinomas of gastric cardia and distal stomach.

During the past decades, the subsites of gastric carcinoma underwent significant changes. The incidence of the adenocarcinoma at distal stomach has been decreased, whereas cardiac adenocarcinoma remained increasing in many countries. The aim of this study was to investigate the differences between gastric cardiac and distal adenocarcinomas. We detected expressions of cytokeratins (cytokeratins 7, 14, 19, and 20) and mucins (mucins 1, 2, and 5AC) by immunohistochemistry and signaling molecules (p38, mitogen-activated protein kinase-interacting kinase 1 (MNK1), extracellular signal-regulated kinase, Jun N-terminal kinase, and phosphoinositide 3 kinase) by reverse transcription-polymerase chain reaction in both groups. The incidence of mucin 2 expression was lower in total (50.0%) and advanced-stage cases (52.0%) with cardiac adenocarcinomas than those in distal cases with total (70.2%) and advanced stage (71.4%), respectively. However, the staining for cytokeratin 14 was also significantly higher in total or advanced-stage tumors from the cardia. Our data showed no significant difference of cytokeratin 7/cytokeratin 20 pattern between 2 groups, but cytokeratin 20 expression was significantly higher in advanced-stage carcinomas of the cardia (58.7%) than in distal ones with advanced stage (38.3%). A multivariate analysis demonstrated different relationships between immunophenotypic markers and pathologic parameters in adenocarcinomas of the cardia and distal stomach. Moreover, significantly lower expressions of MNK1 and p38 in cardiac tumors were also detected. In summary, we found significant differences in patterns of immunophenotypic markers and expressions of signaling molecules between the 2 groups. It is indicated that adenocarcinoma of the cardia was different in histotype and histologic origin from distal adenocarcinoma. The cardiac adenocarcinoma might be a special subtype or an independent entity of gastric carcinoma in China.

[Expression and significance of JNK1, Raf-1 and Livin in the carcinogenesis of sporadic colorectal tubular adenoma].

OBJECTIVE: To study the possible role of JNK1, Raf-1 and Livin in the carcinogenesis of sporadic colorectal tubular adenoma. METHODS: Immunohistochemical staining was used to detect the expression of JNK1, Raf-1 and Livin proteins in 65 sporadic colorectal tubular adenomas with dysplasia of varying degrees and 22 colorectal tubular adenoma with cancerous area. RESULTS: In normal colorectal mucosa, colorectal tubular adenoma with dysplasia and colorectal tubular adenoma with cancerous area, the positive rate of JNK1, Raf-1 and Livin expression was increased gradually. The positive expression of JNK1, Raf-1 and Livin was all significantly higher in the cases of colorectal tubular adenoma with dysplasia or with cancerous area than that in normal colorectal mucosa (P < 0.05), and the positive expression of JNK1, Raf-1 and Livin was significantly higher in colorectal tubular adenoma with cancerous area than that in colorectal tubular adenoma with dysplasia of different degrees (P < 0.05). In the cases of colorectal tubular adenoma with dysplasia of varying degrees, the positive expression of Raf-1 was increased along with the increasing dysplasia degree of colorectal tubular adenoma (P < 0.05). Coexpression of JNK1, Raf-1 and Livin increased gradually in the carcinogenesis of sporadic colorectal tubular adenoma, while positive correlation was found among the expressions of JNK1, Raf-1 and Livin. CONCLUSION: JNK1, Raf-1 and Livin may be involved in the carcinogenesis of sporadic colorectal tubular adenoma.

[Correlation between PPARgamma and VEGF-C expression in extrahepatic cholangioadenocarcinoma (EHCAC) and their prognostic significance].

OBJECTIVE: To evaluate the expression of vascular endothelial growth factor C (VEGF-C) and peroxisome proliferators-activated receptors (PPARgamma) in extrahepatic cholangioadenocarcinoma (EHCAC) and to elucidate its correlation with clinicopathological factors and their significance in prognosis. METHODS: The expressions of PPARgamma and VEGF-C were detected by immunohistochemistry in 69 cases of EHCAC, 12 cases of non-tumor bile duct epithelium, and their relationship to clinicopathological parameters and follow-up were analyzed. RESULTS: The positive rate of PPARgamma expression in 69 cases of EHCAC was 59.4%, significantly higher than that in 12 cases of non-tumor bile duct epithelium (0%), (P < 0.01). The positive rate of VEGF-C in 69 cases of EHCAC was 84.1%, also significantly higher than 16.7% in 12 cases of benign bile duct epithelium (P < 0.05). PPARgamma expression was associated with clinical TNM stage and lymph node metastasis. VEGF-C expression was associated with lymph node metastasis. Cox analysis results showed that portal vein and/or hepatic artery invasion, lymph node metastasis and VEGF-C expression were independent prognostic factors of EHCAC (P < 0.05). CONCLUSION: PPARgamma expression may play an important role during tumorigenesis of extrahepatic cholangioadenocarcinoma. The expressions of PPARgamma and VEGF-C are significantly correlated with the clinicopathological characteristics and biological behavior of EHCAC. Expression of VEGF-C is an independent prognosis factors in EHCAC. The detection of PPARgamma and VEGF-C is valuable for evaluation of prognosis of EHCAC.

[Correlations of polymorphisms in matrix metalloproteinase-3 and -7 promoters to susceptibility to brain astrocytoma].

BACKGROUND & OBJECTIVE: Matrix metalloproteinases (MMPs) are key enzymes involved in tumor development, invasion and metastasis. The single nucleotide polymorphisms (SNPs) in the promoter regions of MMP genes may influence tumor development and progression via modulating mRNA transcription and protein expression. This study was to explore the correlations of the promoter SNPs in MMP-3 and MMP-7 genes to susceptibility to brain astrocytoma. METHODS: The genotype of MMP-3 -1171 5A/6A and MMP-7 -181A/G polymorphisms in 236 patients with brain astrocytoma and 366 healthy controls was detected by polymerase chain reaction-restrictive fragment length polymorphism (PCR-RFLP). RESULTS: The allelotype and overall genotype distribution of MMP-3 SNP among the astrocytoma patients and healthy controls were similar (P>0.05). Stratified by sex, age, and histological grade, the susceptibility to brain astrocytoma among the subjects with 5A/5A and 5A/6A genotypes and the subjects with 6A/6A genotype were similar(P>0.05). The overall genotype distribution of MMP-7 SNP among the astrocytoma patients and healthy controls were significantly different (P = 0.001). Compared with the A/A genotype, both the G/G and the A/G genotypes significantly increased the susceptibility to astrocytoma [sex-and age-adjusted odds ratio (OR) = 2.77 and 1.69, 95% confidence interval (CI)=1.27-6.02 and 1.01-2.84, respectively]. Stratification analysis showed that the G/G genotype significantly increased the susceptibility to astrocytoma in men (adjusted OR = 3.24, 95% CI = 1.12-9.41) and in the individuals younger than 45 years (adjusted OR = 3.16, 95% CI = 1.09-9.16). When stratified by histological grade, the A/G genotype increased the susceptibility to grade II astrocytoma by about 2 folds (adjusted OR = 2.06, 95% CI = 1.05 - 4.05), while the G/G genotype increased the susceptibility to grade II-IV astrocytoma by about 3 folds. CONCLUSION: MMP-7 -181A/G polymorphism may influence the susceptibility to astrocytoma, while MMP-3-1171 5A/6A polymorphism has no correlation to the susceptibility.