Enhanced expression of Fas and FasL modulates apoptosis in the lungs of severe P. falciparum malaria patients with pulmonary edema

Apoptosis mediated by Fas/FasL has been implicated in pulmonary disorders. However, little is known about the relationship between Fas and FasL in the process of lung injury during malaria infection. Paraffin-embedded lung tissues from malaria patients were divided into two groups: those with pulmonary edema (PE) and those without pulmonary edema (non-PE). Normal lung tissues were used as the control group. Cellular expression of Fas, FasL, and the markers of apoptotic caspases, including cleaved caspase-3 and cleaved caspase-8 in the lung tissues were investigated by the immunohistochemistry (IHC) method. Semi-quantitative analysis of IHC staining revealed that cellular expression of Fas, FasL, cleaved caspase-8, and cleaved caspase-3 were significantly increased in the lungs of patients with PE compared with the lungs of patients with non-PE and control groups (all P < 0.05). In addition, significant positive correlations were obtained between Fas and apoptosis (r_s = 0.937, P < 0.001) and FasL and apoptosis (r_s = 0.808, P < 0.001). Significant positive correlations were found between Fas and FasL expression (r_s = 0.827, P < 0.001) and between cleaved caspase-8 and cleaved caspase-3 expression (r_s = 0.823, P < 0.001), which suggests that Fas-dependent initiator and effector caspases, including cleaved caspase-8 and caspase-3, are necessary for inducing apoptosis in the lungs of patients with severe P. falciparum malaria. The Fas/FasL system and downstream activation of caspases are important mediators of apoptosis and may be involved in the pathogenesis of pulmonary edema in severe P. falciparum malaria patients. The proper regulation of the Fas/FasL pathway can be a potential treatment for pulmonary complications in falciparum malaria patients.     

Correlation of RKIP,STAT3 and cyclin D1 expression in pathogenesis of gastric cancer

RKIP is proposed as a new metastasis suppressor. Our recent study showed that RKIP inhibits malignant phenotypes of gastric cancer cells. However, the underlying mechanism of RKIP function in gastric cancer is unclear. This study aimed to investigate the correlation of RKIP, STAT3 and cyclin D1 expression in the tumorigenesis of gastric cancer. RKIP, STAT3 and cyclin D1 proteins were detected by immunohistochemistry in tissues of gastric ulcer (n = 27), gastric adenomatous polyp (n = 7), intestinal metaplasia (n = 26), dysplasia (n = 40), gastric carcinoma (n = 169) and metastatic lymph node (n = 36). RKIP, STAT3 and cyclin D1 mRNA levels were analyzed by RT-PCR in SGC7901 cells. We found that RKIP protein expression was significantly decreased in advanced gastric cancer and metastatic lymph node tissues while cyclin D1 and STAT3 protein expression was markedly increased in severe dysplasia, gastric cancer and metastatic lymph node tissue (P < 0.01). RKIP expression in gastric cancer was negatively correlated with the invasion, TNM stage and lymphoid node metastasis (P < 0.01), while cyclin D1 and STAT3 expression was positively correlated with histological differentiation and lymphoid node metastasis (P < 0.01). RKIP protein level was negatively correlated with cyclin D1 and STAT3 protein level, while cyclin D1 protein level was positively correlated with STAT3 protein level in gastric cancer samples. Moreover, reconstitution of RKIP in SGC7901 gastric cancer cells led to reduced cyclin D1 and STAT3 mRNA levels. In conclusion, these data suggest that RKIP inhibits gastric cancer metastasis via the downregulation of its downstream target genes STAT3 and cyclin D1.     

大肠癌组织中Fas/FasL系统、nm23表达与转移的关系

目的：探讨Fas、FasL和nm23蛋白在大肠癌组织中表达与淋巴结转移和远处肝转移 的关系及临床意义。方法：应用S－P免疫组化法检测80例大肠癌组织和20例正常肠黏膜组织中Fas、FasL及nm23的表达情况。结果：55％大肠癌有不同 程度的Fas表达，低于正常肠黏膜组织中的表达，其表达与Dukes分期密切相关。分期越高，Fas表达率越低，有淋巴结 转移 的C期和有远处肝转移的D期Fas阳性表达率低于无转移的A期和B期，其中D期显著低于AB期，但C期与AB期、C期与D期的表达差异无显著性。大肠癌组织FasL和nm23的表达率分别为68．75％和57．50％，高于正常组织中的表达，表达与有无淋巴结转移或肝转移均无相关性。Fas/FasL系统与nm23表达亦无相关性。结论：Fas/FasL系统中Fas可作为反映大肠癌生物 学行为和判断预后的重要指征，nm23表达增加可能在大肠癌进展早期而不是在进展播散期起重要作用，与其转移与预后无关。     

Expression of SNCG,MAP2, SDF-1 and CXCR4 in gastric adenocarcinoma and their clinical significance

Objectives: The purpose of the study was to detect the expression of SNCG, MAP2, SDF-1 and CXCR4 in gastric adenocarcinoma, and to evaluate their roles in the carcinogenesis of gastric adenocarcinoma, development, invasion and metastasis as well as their clinical significance. Methods: The expression of SNCG, MAP2, SDF-1 and CXCR4 was detected by SP immunohistochemical method in 225 cases of gastric adenocarcinoma and 105 cases of nonneoplastic adjacent gastric tissue. The expression of SNCG, MAP2, SDF-1 and CXCR4 mRNA was also detected by RT-PCR method in 50 cases of gastric adenocarcinoma and 30 cases of nonneoplastic adjacent gastric tissue. Results: The expression of SNCG, MAP2, SDF-1 and CXCR4 in the gastric adenocarcinoma was remarkably higher than those in the nonneoplastic adjacent gastric tissue (P < 0.01); The positive expression of SNCG and MAP2 was correlated with the depth of tumor invasion and the metastasis of lymph nodes (P < 0.05), and that of SDF-1 and CXCR4 was correlated with the metastasis of lymph nodes (P < 0.05). Conclusions: SNCG, MAP2, SDF-1 and CXCR4 may play an important role in the carcinogenesis, progression, invasion and metastasis of gastric adenocarcinoma. However, it still needs more exploration whether they can serve as promising therapeutic targets of gastric adenocarcinoma.     

Down-regulation of neutrophil gelatinase-associated lipocalin in head and neck squamous cell carcinoma correlated with tumorigenesis,not with metastasis

To examine the significance of the Neutrophil gelatinase-associated lipocalin (NGAL) in diagnosing head and neck squamous cell carcinoma (HNSCC) and predicting regional metastasis. We first used GEO dataset to analyze the NGAL gene expression in HNSCC. Then, we summarized the characteristics of patients retrospectively selected in clinic. Expression of NGAL protein in human HNSCC tumor, lymph node and normal samples were analyzed using immunohistochemistry. Next, we further investigated the NGAL expression in a tissue microassay to analyze the relationship between NGAL protein expression and TNM stage. Finally, we tested the NGAL protein expression in head and neck cancer cell lines. Analysis of GEO dataset concluded that NGAL gene expression in HNSCC was lower than that in normal tissue (P<0.01). There was no statistically significant difference of NGAL gene expression between T-stage and N-stage (P>0.05). NGAL protein expression in tumor was lower than that in normal tissue (P<0.01). There was no statistically significant difference of NGAL protein expression between metastasis group and non-metastasis group (P>0.05). Expression of NGAL protein was not correlated with TNM stage of HNSCC. Aggressive HNSCC cell lines have lower NGAL protein expression. Our data demonstrated that the expression of NGAL protein was correlated with tumorigenesis of HNSCC, but not with regional metastasis. It may serve as a novel biomarker for prognostic evaluation of patients with HNSCC.     

Expression and prognostic value of c-Myc and Fas (CD95/APO1) in patients with pancreatic cancer

The identification of molecular prognostic markers for pancreatic cancer patients could provide insightful information for their management in the clinic. The aim of the study is to investigate whether or not the expressions of c-Myc and Fas (CD95/APO1) have prognostic relevance for overall survival (OS) in patients with pancreatic cancer. we used immunohistochemistry on tissue microarrays containing 162 pancreatic cancer specimens to assess the protein expression levels of c-Myc and Fas. Kaplan-Meier survival analysis demonstrated that high level of c-Myc cytoplasmic expression was significantly correlated with worse survival in patients with pancreatic cancer (P = 0.012), while high level of Fas cytoplasmic expression was significantly associated with better outcome of pancreatic cancer (P = 0.046). However, multivariate Cox model analysis showed that tumor differentiation, lymph node status and c-Myc cytoplasmic expression were significant independent prognostic factors for OS (P < 0.001, P = 0.023, P = 0.001, respectively). On the contrary, Fas cytoplasmic expression did not independently influence patient’s prognosis (P = 0.249). Our data suggested that high level of c-Myc cytoplasmic expression may be considered as a valuable marker for prognosis of pancreatic cancer.     

Expression of RKIP,E-cadherin and NF-kB p65 in esophageal squamous cell carcinoma and their correlations

To detect the expression of RKIP, E-cadherin and NF-kB p65 in esophageal squamous cell carcinoma (ESCC) and study their correlations. Steptavidin-peroxidase (S-P) method was employed to detect the expressions of RKIP, E-cadherin and NF-kB p65 in ESCC tissues from 77 cases and paracancerous tissues from 77 cases. The correlations between their expressions and clinicopathological indices and between the expressions of these proteins themselves were analyzed. The expressions of RKIP and E-cadherin in ESCC tissues were obviously lower than those in the paracancerous tissues (P<0.01); the expressions in ESCC tissues from cases with lymph node metastasis were lower than those from cases without lymph node metastasis (P<0.01); the expression of RKIP was positively correlated with the expression of E-cadherin in ESCC tissues (P<0.01). The expression of NF-kB p65 in ESCC tissues was correlated with clinical staging, lymph node metastasis and tumor differentiation (P<0.01); the expression of RKIP was negatively correlated with the expression of NF-kB p65 in ESCC tissues (P<0.05). Downregulation or depletion of RKIP was related to the onset and progression of ESCC, and facilitated the invasion and metastasis of ESCC by downregulating E-cadherin and upregulating NF-kB p65.     

Expression of E-cadherin and vimentin in oral squamous cell carcinoma

The aim of the study is to determine the levels of E-cadherin, vimentin expression in tumor tissues from patients with oral squamous cell carcinoma (OSCC), and the relationship between the expression of E-cadherin, vimentin and epithelial-mesenchymal transition, in order to explore its values for predicting the invasion and metastasis of oral squamous cell carcinoma, short survival of patients in many types of cancer. E-cadherin and vimentin expression of 10 benign and 42 OSCC tumor tissues was examined by immunohistochemical staining. E-cadherin is positively expressed in normal oral mucosa epithelium, but vimentin expression is not found in normal oral mucosa epithelia; the E-cadherin and vimentin were expressed in 26 of 42 (61.9%) and 16 of 42 (38.1%), respectively. No statistically difference was found for E-cadherin and vimentin expression in patients with different age, gender and tumor location, E-cadherin and vimentin expression was significantly associated with lymph node metastasis and tissue location (P < 0.05); E-cadherin expression was also significantly associated with tumor stage (P < 0.05); there are significantly difference between infiltrative margin and central area in patients with oral squamous cell carcinoma for E-cadherin and vimentin positive expression (P < 0.05). E-cadherin and vimentin positive expression was associated with tumor metastasis of oral squamous cell carcinoma. Our study preliminarily confirmed that EMT phenomenon is existed during the development of oral squamous cell carcinoma. Co-evaluation of E-cadherin and vimentin might be a valuable tool for predicting OSCC patient outcome.     

High Fas expression in gastric carcinoma cells as a factor correlating with the occurrence of metastases to regional lymph nodes

PurposeThe aim of this study was to evaluate the correlation of the expression of Fas and Fas-L proteins in gastric carcinoma cells on the occurrence of metastases to regional lymph nodes.Material/methodsThe study included 89 patients treated surgically for gastric carcinoma. The evaluated clinicomorphological parameters were verified based on both histopathological material collected at surgery and intraoperative image. Fas and Fas-L expression was evaluated immunohistochemically in the neoplastic tissue of the removed gastric tumors.ResultsA statistically significant positive correlation between Fas expression in gastric carcinoma cells and the number of regional lymph nodes affected by metastases was observed (p < 0.05). No such correlation was noticed with respect to Fas-L. A statistically significant correlation between the depth of neoplastic infiltration of the stomach wall (T feature) and the number of affected lymph nodes was observed (p < 0.05). No statistically significant correlations in the other examined clinicomorphological features and the number of metastatic lymph nodes was observed.ConclusionA positive Fas expression correlates with more frequent occurrence of metastases to regional lymph nodes. Determination of this protein expression in cancer cells prior to surgery may be helpful for planning the surgical procedure, especially with respect to the extent of lymph node excision.     

Overexpression of eIF3e is correlated with colon tumor development and poor prognosis

EIF3e is a component of the eukaryotic translation initiation factor 3 (eIF-3) complexes, which is an essential factor for initiation of protein synthesis in mammalian cells. Translational control plays key roles in the complex mechanism of cancer development and progression. However, the clinical significance of eIF3e in colon cancer remains to be elucidated. We analyzed the eIF3e expression in a tissue microarray (TMA), which contained 173 colon cancer tissues paired with adjacent normal mucosa and lymph node metastasis. The expression of eIF3e was significantly elevated in colon cancer tissues in comparison with those in adjacent normal mucosa (P < 0.001) and lymph node metastasis (P < 0.001). The high expression of eIF3e in colon cancer was significantly correlated with tumor size (P < 0.001), lymph node involvement (P < 0.001), distant metastasis (P < 0.001), clinical stage (P < 0.001), histopathologic classification (P < 0.001), and vessel invasion (P = 0.036). Univariate and multivariate analysis revealed that eIF3e is an independent prognosis factor for overall survival and disease-free survival in colon cancer. Down-regulation of eIF3e in vitro inhibited colon cancer cell proliferation, clonality and promoted cell apoptosis. Taken together, high eIF3e expression may contribute to tumor progression and predict poor prognosis in colon cancer.     

Decreased expression of SEMA3A is associated with poor prognosis in gastric carcinoma

Background/purpose: SEMA3A (semaphorin-3A), is a secreted protein that belongs to the semaphorin family and can function as both a chemoattractive agent or a chemorepulsive agent. SEMA3A has been shown to be a tumor suppressor in various cancers. This study investigated the expression of SEMA3A in gastric cancer and its prognostic value for gastric cancer patients. Methods: We examined the expression of SEMA3A in paired cancerous and matched adjacent noncancerous gastric mucosa tissues by real-time quantitative RT-PCR (qRT-PCR) and western blotting. In vitro, we evaluate the effects of SEMA3A on gastric cancer cell proliferation and migration by MTT, transwell and wound-healing assays. Furthermore, we analyzed SEMA3A expression in 128 patients who underwent resection procedures using immunohistochemistry. The relationships between the SEMA3A expression levels, the clinicopathological factors, and patient survival were investigated. Results: Our results revealed decreased SEMA3A mRNA (P = 0.0037) and protein (P = 0.033) expression in tumor tissue samples compared with matched adjacent non-tumorous tissue samples. Overexpression of SEMA3A inhibits gastric cancer cell proliferation and migration in vitro. Immunohistochemical staining data showed that SEMA3A expression was significantly decreased in 54.68% of gastric cancer cases. In addition, the chi-square test revealed that low SEMA3A expression was significantly correlated with poor differentiation (P = 0.015), Vascular invasion (P = 0.001), depth of invasion (P < 0.001), lymph node metastasis (P = 0.029), distant metastasis (P = 0.002) and advanced TNM stage (P = 0.003). SEMA3A expression was positively correlated with clinical TNM stage, that suggested the more advanced clinical TNM stage corresponding to the lower expression level of SEMA3A (r_s = -0.322, P < 0.001) by Spearman rank correlation analysis. Kaplan-Meier survival analysis demonstrated that low expression of SEMA3A was significantly correlated with a poor prognosis for gastric cancer patients (P < 0.001). The multivariate analysis revealed that SEMA3A expression was an independent prognostic factor of the overall survival rate of patients with gastric cancer. Conclusion: SEMA3A expression decreased significantly as gastric cancer progressed and metastasized, suggesting that SEMA3A might serve as a candidate tumor suppressor and a potential prognostic biomarker in gastric carcinogenesis.     

Distinct different sensitivity of Treg and Th17 cells to Fas-mediated apoptosis signaling in patients with acute coronary syndrome

Objective: An imbalance in CD4⁺CD25⁺ regulatory T (Treg) cells and Th17 cells has been found to correlate to occurrence of acute coronary syndrome [ACS, including unstable angina (UA) and acute myocardial infarction (AMI)]. However, the mechanisms of Th17/Treg imbalance in ACS patients are still unclear. The purpose of this study is to investigate the possibility of differences in sensitivity of Th17 and Tregs to Fas-mediated apoptosis which could lead to Th17/Treg imbalance in ACS patients. Methods: We examined the apoptosis of Th17 and Treg cells, apoptosis-related Fas/Fas ligand(FasL) pathway, and inflammatory markers in patients with AMI, UA, stable angina (SA) and controls by Flow cytometry and ELISA. Then we analysed the correlation of inflammatory markers and sFasL to Treg apoptosis, and the effect of anti-FasL antibody on Treg apoptois in vitro. Results: Our study demonstrated that apoptotic Tregs, Fas and FasL expression, Caspase-3 activity of Tregs were significantly higher in ACS patients than those in NCA and SA patients (all P < 0.05). The percentage of apoptotic Tregs is positively correlated with the levels of inflammatory markers and sFasL. In vitro incubation of peripheral blood mononuclear cells from ACS patients with anti-FasL antibody resulted in a markedly reduction of apoptotic Treg cells. However, there were no significant differences in apoptotic Th17 cells and in Fas and FasL expression for Th17 cells between the four groups (all P >0.05). Conclusions: Tregs, but not Th17 cells, become apoptotic through Fas/FasL pathway, which contributed to reduction of Tregs leading to an imbalance between Th17 and Treg cells. This could be the mechanism underlying Th17/Treg imbalance and occurrence of ACS.     

Mixed Carcinoma as an Independent Prognostic Factor in Submucosal Invasive Gastric Carcinoma

Mixed carcinoma shows a mixture of glandular and signet ring/poorly cohesive cellular histological components and the prognostic significance of each component is not fully understood. This study aimed to investigate the significance of the poorly cohesive cellular histological component as a risk factor for lymph node metastasis and to examine the diagnostic reliability of endoscopic biopsy. Clinicopathologic characteristics of 202 patients who underwent submucosal invasive gastric carcinoma resection with lymph node dissection in 2005–2012 were reviewed. Mixed carcinoma accounted for 27.2% (56/202) of cases. The overall prevalence of lymph node metastasis was 17.3% (35/202). Lymphatic invasion (P < 0.001), family history of carcinoma (P = 0.025), tumor size (P = 0.004), Lauren classification (P = 0.042), and presence of any poorly cohesive cellular histological component (P = 0.021) positively correlated with the lymph node metastasis rate on univariate analysis. Multivariate analyses revealed lymphatic invasion, family history of any carcinoma, and the presence of any poorly cohesive cellular histological component to be significant and independent factors related to lymph node metastasis. Review of preoperative biopsy slides showed that preoperative biopsy demonstrated a sensitivity of 63.6% and a specificity of 100% in detecting the presence of the poorly cohesive cellular histological component, compared with gastrectomy specimens. The presence of any poorly cohesive cellular histological component was an independent risk factor associated with lymph node metastasis in submucosal invasive gastric carcinoma. Endoscopic biopsy had limited value in predicting the presence and proportion of the poorly cohesive cellular histologic component due to the heterogeneity of mixed carcinoma.     

Up-regulation of Fas ligand (FasL) mRNA expression in peripheral blood mononuclear cells (PBMC) after major surgery

FasL, which is expressed mainly on activated lymphocytes, can induce apoptosis (programmed cell death) of cells which express Fas. Fas/FasL interaction is primarily beneficial in maintaining immunological and physiological homeostasis by eliminating unnecessary cells. Dysregulation of the interaction, however, leads to tissue damage. We investigated how Fas/FasL levels changed after major surgery. The major aim of this study was to elucidate the involvement of the Fas/FasL system in postoperative inflammation. The investigation involved 10 patients admitted to the intensive care unit after surgery. Although the percentage of Fas⁺ cells and the amount of Fas expression tended to increase, there was no significant difference between pre- and post-operative samples. In contrast, the levels of FasL mRNA were dramatically up-regulated after operation. Post-operative C-reactive protein (CRP) levels increased and correlated well with FasL levels (r = 0.91, P < 0.01). Lymphocyte counts decreased after operation and were inversely proportional to FasL levels (r = 0.58, P < 0.05). These results suggest that the enhanced FasL expression is likely to be related to systemic inflammatory responses induced during the perioperative period. FasL up-regulation may be involved in the aggravation of tissue damage, including lymphocytopenia, in the early post-operative period.     

Coelomic cells show apoptosis via Fas/FasL system: a comparative study between healthy human pregnancies and missed miscarriages

BACKGROUND: The Fas/Fas ligand (FasL) system represents one of the mainapoptotic pathways controlling placental apoptosis throughoutgestation. In the current study, we have examined the Fas/FasLprotein expression and the apoptotic incidents of coelomic cells,amniotic cells and trophoblastic tissue in first trimester humanpregnancies and missed miscarriages (MM). METHODS: Protein expression was determined by immunofluoresence, westernblotting analysis, immunohistochemistry and indirectly by RT–PCR,whereas apoptotic cell death was assessed by in situ DNA fragmentationanalysis. RESULTS: Coelomic cells express Fas/FasL proteins, can undergo apoptosisand were the only cells in which apoptosis, Fas protein expressionand FasL protein expression were accordingly increased alongwith gestational age (P = 0.001, P = 0.008; P = 0.012, respectively).In contrast, amniotic cells and trophoblast showed a consistencyin the expression levels of Fas/FasL proteins in healthy pregnancies.MM were accompanied by increased Fas/FasL protein expressionin all examined samples (P < 0.001). The increase of Fas/FasLprotein expression was accompanied by proportional increaseof apoptotic incidents among the coelomic cell population (P= 0.023, P = 0.009, respectively), whereas amniotic cells andtrophoblast appeared to be resistant to Fas-induced apoptosis.The lowest expression of Fas/FasL proteins and the minimum occurrenceof apoptotic incidents were detected in the trophoblast. CONCLUSIONS: These data suggest that there is a different regulation andfunction of the Fas/FasL system in early human pregnancies.Aberration of the Fas-mediated apoptosis may represent one ofthe execution-step necessary for pregnancy loss in MM cases.     

Expression of livin,survivin and caspase-3 in prostatic cancer and their clinical significance

To explore the expressions level of Livin, Survivin and Caspase-3 in prostatic cancer and the relationship among the 3 proteins and the clinicopathological features as well as the correlation among them. Totally, 43 paraffin-embedded prostate cancer tissues obtained from patients who were performed with rectal prostate biopsy or excision and 17 paraffin-embedded prostatic hyperplasia tissues were collected. All the specimens were confirmed by pathology. Immunohistochemistry SP method was used to detect the expressions of Livin, Survivin and Caspase-3 in prostatic cancer compared to hyperplasia tissues. The positive expression rates of both Livin and Survivin in prostatic cancer tissue were higher than those in prostatic hyperplasia tissue (93.02% vs. 64.70%, P < 0.05; 83.72% vs. 35.29%, P < 0.01). However, the positive expression rate of Caspase-3 in prostatic cancer tissue was obviously lower than that in prostatic hyperplasia tissue (25.58% vs. 58.82%, P < 0.01). Both Livin and Survivin expressions in prostatic cancer tissue were related to pathological grading (Gleason scores) (X² = 14.000, P = 0.001), but not related to preoperative PSA, clinical stages and distant metastasis (P > 0.05). Capsase-3 expression in prostatic cancer tissue was related to pathological grading (Gleason scores) (X ² = 14.000, P = 0.001) and clinical stages (X ² = 4.896, P = 0.027), but not related to preoperative PSA and distant metastasis (P > 0.05). In prostatic cancer tissue, Livin expression had no correlation with Survivin expression (r = 0.127, P = 0.419 > 0.05), but negatively correlated with Caspase-3 expression (r = -0.497, P = 0.001). Survivin expression was negatively correlated with Caspase-3 expression (r = -0.354, P = 0.020). Livin, Survivin and Caspase-3 are closely related to the occurrence and development of prostatic cancer and which are expected to become new targets for diagnosis and treatment in future.     

Correlation and prognostic significance of MMP-2 and TFPI-2 differential expression in pancreatic carcinoma

Aberrant expression of matrix metalloproteinase (MMP)-2 and tissue factor pathway inhibitor (TFPI)-2 not only correlate with tumorigenesis, but also with tumor invasion and metastasis. This study aims to investigate the correlation and prognostic significance of MMP-2 and TFPI-2 differential expression in pancreatic carcinoma. Immunohistochemistry was used to evaluate MMP-2 and TFPI-2 expression in tumor tissues and corresponding non-tumor tissues from 122 patients with pancreatic carcinoma. The results showed that the expression of MMP-2 was significantly (P < 0.05) higher in tumor tissues (78.7%) than in adjacent non-tumor tissues (27.9%), whereas the expression of TFPI-2 was significantly (P < 0.001) lower in tumor tissues (27.9%) than in adjacent non-tumor tissues (79.5%). Spearman’s rank correlation test showed a negative correlation between MMP-2 and TFPI-2 expression (r = -0.346, P < 0.001). Kaplan-Meier survival analysis showed that high MMP-2 expression was significantly correlated with decreased disease-free survival (DFS) (P < 0.001) and overall survival (OS) (P < 0.001), while high TFPI-2 expression was significantly associated with increased DFS (P < 0.001) and OS (P < 0.001) of the patients. Multivariate analysis showed that high MMP-2 expression can act as an independent predictive factor for poor DFS (P = 0.01); and low TFPI-2 expression as an independent prognostic factor for poor DFS (P < 0.001) and OS (P < 0.001). In conclusion, our findings suggested that the differential expression of MMP-2 and TFPI-2 have a negative correlation in pancreatic carcinoma tissues; they may be considered as valuable biomarkers for prognosis of pancreatic carcinoma.     

Overexpression of cytokeratin 17 is associated with the development of papillary thyroid carcinoma and the presence of lymph node metastasis

Cytokeratin 17 (CK17), a basal/myoepithelial cell keratin, appears to play an important role in the progression of several human malignancies. Increased CK17 expression has previously described in cases of papillary thyroid carcinoma (PTC). However, no studies to date have investigated the clinical significance of CK17 expression in patients with PTC. The aim of this study was to compare the expression of CK17 in patients with PTC with that observed in normal thyroid tissue and benign thyroid lesions, and to examine the relationship between CK17 expression and clinicopathologic characteristics of patients with PTC. CK17 protein expression was evaluated by immunohistochemistry on tissue microarrays containing thyroid tissue samples from 108 PTCs, 16 nodular goiters, and 81 healthy controls. Sixty-five of the 108 (60.2%) PTC tissue samples exhibited positive CK17 expression, whereas all nodular goiters and normal thyroid tissue samples showed a complete absence of CK17 immunoreactivity. The difference in frequency of CK17 positivity between PTC (65/108, 60.2%), normal thyroid tissue (0/81, 0.0%), and benign thyroid lesions (0/16, 0.0%) was statistically significant (P<0.001). Positive CK17 expression in PTC was significantly associated with the presence of lymph node metastasis (P=0.024) and higher pN stage (P=0.028). Expression of CK17 is significantly increased in cases of PTC compared to normal tissue and benign thyroid lesions, and CK17 overexpression is associated with the presence of lymph node metastasis in patients with PTC. These findings suggest that CK17 is involved in the development and metastasis of PTC.