Management of Combined Atlas Fracture with Type II Odontoid Fracture: A Review of 21 Cases.

PURPOSE: To evaluate the therapeutic effects of combined atlas fracture with type II (C1-type II) odontoid fractures and to outline a management strategy for it. PATIENTS AND METHODS: Twenty three patients with C1-type II odontoid fractures were treated according to our management strategy. Nonoperative external immobilization in the form of cervical collar and halo vest was used in 13 patients with stable atlantoaxial joint. Surgical treatment was early performed in 10 patients whose fractures with traumatic transverse atlantal ligament disruption or atlantoaxial instability. The visual analog scale (VAS), neck disability index (NDI) scale, and American Spinal Injury Association (ASIA) scale at each stage of followup were then collected and compared. RESULTS: Compared to pretreatment, the VAS score, NDI score, and ASIA scale were improved among both groups at followup evaluation after treatment. However, in the nonsurgical group, one patient (1/11) developed nonunion which required surgical treatment in later stage and one patient (1/13) with halo vest immobilization had happened pin site infection. Two patients of the surgical group (2/11) had appeared minor complications: occipital cervical pain in one case and cerebrospinal fluid leakage in one case. Two patients (2/23) were excluded from nonsurgical treatment group because their followup period was less than 12 months. Twenty one patients were followed up regularly with an average of 23.9 months (range 15-45 months). CONCLUSIONS: We outlined our concluding management principle for the treatment of C1-type II odontoid fractures based on the nature of C1 fracture and atlantoaxial stability. The treatment principle can obtain satisfactory results for the management of C1-type II odontoid fractures.

Up-regulation of long noncoding RNA M26317 correlates with tumor progression and poor prognosis in gastric cancer.

To investigate the expression and clinical significance of long noncoding RNA (lncRNA) in gastric cancer, we applied microarray analysis to obtain expression profiles of protein-coding genes and lncRNAs in tumor and paired adjacent nontumor tissues. We found that 41 lncRNAs were up-regulated and 31 lncRNAs were down-regulated more than 2-fold in gastric cancer versus noncancerous tissues (ratio >2.0, P < .01). We established a coexpression network of the differentially expressed lncRNAs and targeted coding genes that included 17 lncRNAs and 16 coding genes. Because the results of microarray analysis showed that lncRNA M26317 was up-regulated in gastric cancer tissues, we examined the expression level of M26317 in 103 gastric cancer tissues by reverse-transcription polymerase chain reaction and 436 gastric cancer tissues by in situ hybridization. Our data confirmed that M26317 was up-regulated in gastric cancer tissues. Moreover, expression of M26317 correlated with patient age, size of tumor, Lauren's classification, depth of invasion, lymph node and distant metastasis, TNM stage, and poor prognosis (P < .05), but was not associated with sex, location of tumor, and differentiation (P > .05). M26317 may have an important role in malignant transformation and metastasis of gastric cancer.

Metastasis-associated protein 1 (MTA1) in gastric cancer tissues is positively associated with poorer prognosis.

BACKGROUND: The present study examined the clinical significance of metastasis-associated protein 1 (MTA1) in the progression and patient survival of gastric cancer. METHODS: Paraffin-embedded resected tissues of gastric cancer mucosa (n = 436) and adjacent normal mucosa (n = 92) were assessed immunohistochemically for MTA1 protein, and scored according to the percentage of cells positively stained for MTA1 combined with stain intensity. Associations between MTA1 staining scores and clinicopathological factors, including survival time, were evaluated. RESULTS: The staining scores for MTA1 were significantly higher in gastric cancer tissues than in matched normal tissues. MTA1 scores positively correlated with tumor size, depth of invasion, presence of lymph node metastasis, lymphatic involvement, venous invasion, distal metastasis, and advanced clinical staging. Patients with high MTA1 scores in gastric cancer tissues had a significantly lower five-year survival rate compared with patients with low MTA1 scores. The multivariate analysis indicated that MTA1 protein levels in resected gastric cancer tissues, as reflected by immunohistochemical staining, are an independent prognostic index of gastric carcinoma (P < 0.01). CONCLUSION: MTA1 immunopositivity was significantly associated with progression of gastric cancer, and may be helpful in gastric cancer prognosis.

CEACAM6 is a prognostic biomarker and potential therapeutic target for gastric carcinoma.

This study aims to investigate the prognostic power of carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) in gastric cancer (GC) and its potential role in cancer development and progression. Data mining results show that CEACAM6 is overexpressed in gastric cancer and is correlated with lymph node metastasis. Subsequently, immunohistochemical staining was performed to determine CEACAM6 protein levels in paraffin gastric tumor specimens. Real-time reverse-transcription-polymerase chain reaction (RT-PCR) was conducted to detect CEACAM6 mRNA levels in fresh GC samples. CEACAM6 protein and mRNA levels were significantly up regulated in GC compared with paired normal mucosa. The IHC staining intensity of CEACAM6 was positively correlated with tumor size, Lauren's classification, vascular invasion, lymph node metastasis, distant metastasis, and TNM stage. CEACAM6 expression was inversely correlated with the five-year survival rate of GC patients. Cox multivariate analysis results demonstrated that the overall survival was independently correlated with CEACAM6 expression. A significant association was observed between CEACAM6 and distant metastases. Network analysis of downstream gene signatures revealed several hub genes such as SRC and DNM1L etc. which may mediating tumor promoting functions of CEACAM6. Further data mining discovered that Tamoxifen etc. could be therapeutic alternatives for gastric patients with CEACAM6 overexpression. Collectively, CEACAM6 overexpression is a common characteristic of GC and is associated with poor 5 year survival rate in GC. Besides, potential molecular mechanisms and treatment options were also provided.

Clinical and radiological outcomes following hybrid surgery in the treatment of multi-level cervical spondylosis: over a 2-year follow-up.

BACKGROUND: The optimal surgical approach for treatment of multi-level cervical disc disease is currently widely debated. Anterior cervical discectomy and fusion (ACDF) combined with cervical disc arthroplasty (CDA) has been presented as a treatment approach, but to date, there are few reports with adequate clinical and radiological data for this hybrid surgical procedure. The goal of this paper is to assess clinical and radiological outcomes in patients with cervical spondylosis in three contiguous segments after treatment with artificial disc replacement combined with fusion. MATERIALS AND METHODS: We performed a retrospective review of 36 patients (mean age of 48.6 years) with contiguous three-level cervical spondylosis who were treated with ACDF coupled with CDA (hybrid surgery) between October 2008 and October 2012. Clinical evaluation was based on the Neck Disability Index (NDI), Japanese Orthopaedic Association (JOA) score, and postoperative JOA score improvement rate (IR). Radiographic parameters, angular range of motion (ROM) for C2-C7, and ROM for the superior and inferior adjacent segments were measured before the operation, at 1, 3, 6, and 12 months postoperation, and at the final follow-up evaluation. All cases were followed for at least 28 months (range 28-65 months). RESULTS: All patients exhibited significant postoperative improvement in NDI and JOA scores compared to preoperative levels (P < 0.05), and these improved scores were maintained during the follow-up period. The JOA score improvement rate was 70.83 % at the final follow-up evaluation. The mean C2-C7 ROM of all cases was significantly decreased immediately after operation but recovered to preoperative levels after 12 months (P = 0.721). The ROM of the superior and inferior adjacent segments was recovered to preoperative levels after 6 months (P > 0.05). One patient required a second surgery for symptomatic adjacent segment degeneration. Neither pseudarthrosis nor other device migration was observed in any patients during the entire follow-up period. CONCLUSIONS: These results indicate that hybrid surgery seems to be a promising, acceptable, and alternative surgical approach for the treatment of multi-level cervical disc disease.

MicroRNA-10b promotes migration and invasion through Hoxd10 in human gastric cancer.

BACKGROUND: This study aims to investigate the effect of miR-10b overexpression on cancer cell proliferation, migration, invasion, and Hoxd10 expression. METHODS: The effect of miR-10b on proliferation, migration, and invasion of MKN-28, BGC-823, and SGC-7901 cells and the expression of Hoxd10 protein in SGC-7901 and BGC-823 cells were detected following transfection of miR-10b inhibitor or Negative Control B. Expression of Hoxd10 protein in 436 paraffin-embedded cancer tissues was also investigated. RESULTS: miR-10b was significantly upregulated in AGS, MKN-28, BGC-823, HCG-27, SGC-7901, and MKN-45 cell lines, miR-10b inhibitor significantly inhibited proliferation and migration of MKN-45, BGC-823 and SGC-7901 cells 48 h after transfection, while Hoxd10 protein in these cells lines had increased 72 h after transfection. Hoxd10 was highly expressed in gastric cancer and correlated with size of tumor, Lauren classification, depth of invasion, lymph node and distant metastasis, Tumor-Node-Metastasis (TNM) stage, and prognosis. CONCLUSIONS: miR-10b promotes migration and invasion through Hoxd10 in human gastric cancer cell lines and may play an important role in tumorigenesis, progression, and prognosis.

Recurrent TERT promoter mutations identified in a large-scale study of multiple tumour types are associated with increased TERT expression and telomerase activation.

BACKGROUND: Several somatic mutation hotspots were recently identified in the telomerase reverse transcriptase (TERT) promoter region in human cancers. Large scale studies of these mutations in multiple tumour types are limited, in particular in Asian populations. This study aimed to: analyse TERT promoter mutations in multiple tumour types in a large Chinese patient cohort, investigate novel tumour types and assess the functional significance of the mutations. METHODS: TERT promoter mutation status was assessed by Sanger sequencing for 13 different tumour types and 799 tumour tissues from Chinese cancer patients. Thymic epithelial tumours, gastrointestinal leiomyoma, and gastric schwannoma were included, for which the TERT promoter has not been previously sequenced. Functional studies included TERT expression by reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR), telomerase activity by the telomeric repeat amplification protocol (TRAP) assay and promoter activity by the luciferase reporter assay. RESULTS: TERT promoter mutations were highly frequent in glioblastoma (83.9%), urothelial carcinoma (64.5%), oligodendroglioma (70.0%), medulloblastoma (33.3%) and hepatocellular carcinoma (31.4%). C228T and C250T were the most common mutations. In urothelial carcinoma, several novel rare mutations were identified. TERT promoter mutations were absent in gastrointestinal stromal tumour (GIST), thymic epithelial tumours, gastrointestinal leiomyoma, gastric schwannoma, cholangiocarcinoma, gastric and pancreatic cancer. TERT promoter mutations highly correlated with upregulated TERT mRNA expression and telomerase activity in adult gliomas. These mutations differentially enhanced the transcriptional activity of the TERT core promoter. CONCLUSIONS: TERT promoter mutations are frequent in multiple tumour types and have similar distributions in Chinese cancer patients. The functional significance of these mutations reflect the importance to telomere maintenance and hence tumourigenesis, making them potential therapeutic targets.

MiR-125b promotes cell migration and invasion by targeting PPP1CA-Rb signal pathways in gastric cancer, resulting in a poor prognosis.

BACKGROUND: MiR-125b functions as an oncogene in many cancers; however, its clinical significance and molecular mechanism in gastric cancers have never been sufficiently investigated. Here, we elucidated the functions and molecular regulated pathways of MiR-125b in gastric cancer. METHODS: We investigated MiR-125b expression in fresh tissues from 50 gastric cancer patients and 6 gastric cancer cell lines using RT-PCR, and explored its prognostic value by hybridizing MiR-125b in situ for 300 clinical gastric tumor tissues with pathological diagnosis and clinical parameters. The effects of MiR-125b on gastric cancer cells and downstream target genes and proteins were analyzed by MTT, transwell assay, RT-PCR, and western blot on the basis of silencing MiR-125b in vitro. Luciferase reporter plasmid was constructed to demonstrate MiR-125b's direct target. RESULTS: MiR-125b was upregulated in gastric cancer tissues and cell lines, and significantly promoted cellular proliferation, migration, and invasion by downregulating the expression of PPP1CA and upregulating Rb phosphorylation. MiR-125b expression was significantly correlated with tumor size and depth of invasion, lymph nodes, distant metastasis, and TNM stage. The high-MiR-125b-expression group had a significantly poorer prognosis than the low-expression group (P < 0.05) in stages I, II, and III, and the 5-year survival rate in of the high-expression group was significantly lower than that of the low-expression group. CONCLUSIONS: MiR-125b functions as an oncogene by targeting downregulated PPP1CA and upregulated Rb phosphorylation in gastric cancer. MiR-125b not only promotes cellular proliferation, migration, and invasion in vitro, but also acts as an independent prognostic factor in gastric cancer.

Overexpression of Nedd9 is a prognostic marker of human gastric cancer.

The present study was designed to evaluate the expression and prognostic significance of neural precursor cell-expressed, developmentally downregulated 9 (Nedd9) in patients with gastric cancer. Overexpression of Nedd9 was detected in a number of human cancers and was associated with progression and poor prognosis of the diseases. The expression of Nedd9 and focal adhesion kinase (FAK) were detected using the tissue microarray technique and immunohistochemical method and compared with clinicopathological parameters of patients with gastric cancer. The expressions of Nedd9 and FAK were upregulated in gastric cancer lesions compared with their expression in adjacent non-malignant tissues. High expression of Nedd9 correlated with age, location of tumor, tumor size, depth of invasion, vessel invasion, lymph node metastasis, and distant metastasis, and also with expression of FAK. Further, multivariate analysis suggested that expression of Nedd9 and FAK were independent prognostic indicators for gastric cancer. Cumulative 5-year survival rates of patients with high expression of both Nedd9 and FAK was significantly lower than those with low expression of both. Nedd9 was implicated in the progression of gastric cancer. Based on the TNM stage, Nedd9 and FAK proteins could be useful prognostic marker to predict tumor progression and prognosis in gastric cancer.

The expression of TMPRSS4 and Erk1 correlates with metastasis and poor prognosis in Chinese patients with gastric cancer.

PURPOSE: The present study investigated the clinical significance of transmembrane protease, serine 4(TMPRSS4) and extracellular signal-regulated kinases 1 (Erk1) in the development, progression and metastasis of gastric cancer. METHODS: Immunohistochemistry was employed to analyze TMPRSS4 and Erk1 expression in 436 gastric cancer cases and 92 non-cancerous human gastric tissues. RESULTS: Protein levels of TMPRSS4 and Erk1 were up-regulated in gastric cancer lesions compared with adjacent noncancerous tissues. High expression of TMPRSS4 correlated with age, size, Lauren's classification, depth of invasion, lymph node and distant metastases, regional lymph node stage and TNM stage, and also with expression of Erk1. In stages I, II and III, the 5-year survival rate of patients with high TMPRSS4 expression was significantly lower than in patients with low expression. Further multivariate analysis suggests that up-regulation of TMPRSS4 and Erk1 were independent prognostic indicators for the disease, along with depth of invasion, lymph node and distant metastasis and TNM stage. CONCLUSIONS: Expression of TMPRSS4 in gastric cancer is significantly associated with lymph node and distant metastasis, high Erk1 expression, and poor prognosis. TMPRSS4 and Erk1 proteins could be useful markers to predict tumor progression and prognosis of gastric cancer.

Clonality analysis of neuroendocrine cells in gastric adenocarcinoma.

AIM: To achieve a better understanding of the origination of neuroendocrine (NE) cells in gastric adenocarcinoma. METHODS: In this study, 120 cases of gastric adenocarcinoma were obtained. First, frozen section-immunohistochemistrical samples were selected from a large quantity of neuroendocrine cells. Second, laser capture microdissection was used to get target cells from gastric adenocarcinoma and whole genome amplification was applied to get a large quantity of DNA for further study. Third, genome-wide microsatellite abnormalities [microsatellite instability (MSI), loss of heterozygosity (LOH)] and p53 mutation were detected by polymerase chain reaction (PCR)-single-strand conformation polymer- phism-silver staining and PCR-sequencing in order to identify the clonality of NE cells. RESULTS: The total incidence rate of MSI was 27.4%, while LOH was 17.9%. Ten cases had a highest concordance for the two types of cells. The other samples had similar microsatellite changes, except for cases 7 and 10. Concordant p53 mutations exhibited in sample 4, 14, 21 and 27, and there were different mutations between two kinds of cells in case 7. In case 17, mutation took place only in adenocarcinoma cells. p53 mutation was closely related with degree of differentiation, tumor-node-metastasis stage, vessel invasion and lymph node metastasis. In brief, NE and adenocarcinoma cells showed the same MSI, LOH or p53 mutation in most cases (27/30). In the other three cases, different MSI, LOH or p53 mutation occurred. CONCLUSION: NE and the gastric adenocarcinoma cells may mainly derive from the same stem cells, but the remaining cases showing different origin needs further investigation.

Abnormal expression of miR-301a in gastric cancer associated with progression and poor prognosis.

BACKGROUND AND OBJECTIVES: miR-301a is significantly overexpressed in many cancers. However, its expression and biological role in gastric cancer remain poorly understood. We investigated microRNA-301a (miR-301a) expression in gastric cancer and determined its effects on cancer cell behavior and its clinical significance in the development and progression of gastric cancer. METHODS: We determined miR-301a expression in gastric tumors and gastric cancer cell lines by reverse transcription-polymerase chain reaction. The effects of miR-301a on cell clone formation, migration, and invasion of HGC-27 and SGC-7901 cells were detected following transfection of an miR-301a inhibitor. miR-301a expression in a 304-tissue gastric cancer microarray was determined by in situ hybridization and its role in progression and prognosis was analyzed. RESULTS: miR-301a was upregulated in gastric tumor tissues and cell lines. Down-regulation of miR-301a significantly inhibited cell clone formation, migration, and invasion of HGC-27and SGC-7901 cells. Overexpression of miR-301a in primary gastric cancer tissues was associated with tumor size, invasion depth, lymph node metastasis, and TNM stage. CONCLUSIONS: miR-301a overexpression correlated with TNM stage and prognosis, suggesting that miR-301a is involved in cellular clone formation, migration, and invasion in vitro and may play an important role in the clinical progression and prognosis of gastric cancer.

Prognostic value and clinical pathology of MACC-1 and c-MET expression in gastric carcinoma.

This study was to assess the expression of MACC-1 and c-MET in gastric cancer, and to correlate this expression with clinicohistological parameters and patient prognosis. Total RNA was extracted from cancer tissue and adjacent normal mucosa from frozen biopsy specimens of 30 patients with gastric cancer, and MACC-1 expression was assessed by RT-PCR. MACC-1 and c-MET protein expression were also assessed in paraffin-embedded tissues obtained from 436 tumor mucosa and 92 normal mucosa specimens by immunohistochemistry. The correlation between MACC-1 and c-MET expression and clinicopathological factors (age, sex, histology, tumor depth, lymph node status and vessel invasion) were also evaluated. RT-PCR analysis revealed that MACC-1 expression was significantly higher in cancerous mucosa compared with normal tissue. Immunohistochemical analysis indicated that MACC-1 and c-MET were moderately or strongly expressed in gastric cancer tissue, whereas expression was weak or absent in non-cancer tissue. Expression of MACC-1 or c-MET was significantly associated with larger tumor size, deeper tumor invasion, presence of lymph node metastasis, lymphatic involvement, venous invasion, distant metastasis and advanced clinical stage. However, only MACC-1 exhibited significantly greater expression in carcinomas from the higher age group. The intensity of MACC-1 and c-MET expression was also positively correlated. Survival analysis of the 436 gastric cancer patients revealed that patients in clinical stages I, II and III exhibiting lower MACC-1 and c-MET expression had a higher 5-year survival rate compared with patients expressing high levels of these proteins. Multivariate analysis revealed that MACC-1 and c-MET may be independent prognostic indexes of gastric carcinoma (P < 0.01). Our findings confirm that MACC-1 and c-MET expression is strongly related to gastric cancer stage and degree of malignancy, and is inversely correlated to patient prognosis. Thus, MACC-1 and c-MET may interact to promote tumorigenesis and their expression may be used as independent prognostic markers in gastric cancer.

[Detection and clinicopathologic significance of microsatellite alteration and p53 mutation of neuroendocrine cells in colorectal adenocarcinoma].

OBJECTIVE: To study the possible clonal origin of neuroendocrine cells in colorectal adenocarcinoma. METHODS: Twenty-six microsatellite loci were screened using laser capture microdissection, DNA extraction and whole genome amplification. Microsatellite instability (MSI) and loss of heterozygosity (LOH) in adenocarcinoma cells and neuroendocrine cells amongst 30 cases of colorectal carcinoma with neuroendocrine differentiation were detected using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP)-silver staining. The mutation status of p53 was evaluated by PCR-sequencing. The clonal origin of neuroendocrine cells in colorectal adenocarcinoma was determined. RESULTS: Amongst the 30 cases studied, the prevalence of MSI was 16.9% while that of LOH was 8.5%. The rate showed no statistically significant difference between adenocarcinoma cells and neuroendocrine cells. In 6 cases, the microsatellite alteration was entirely consistent. In 23 cases, the rate of microsatellite alteration consistency was greater than that of inconsistency. In 1 case, the consistency and inconsistency rates were identical. There was statistically significant difference between consistency and inconsistency of microsatellite alteration. The prevalence of p53 mutation was 16.7% which was the same for both adenocarcinoma cells and neuroendocrine cells. CONCLUSIONS: Adenocarcinoma cells and neuroendocrine cells in colorectal adenocarcinoma with neuroendocrine differentiation have similar biologic changes. It is likely that they are of identical origin.

Clinical utility of measuring expression levels of KAP1, TIMP1 and STC2 in peripheral blood of patients with gastric cancer.

BACKGROUND: We examined preoperative kinesin II-associated protein (KAP1), TIMP metallopeptidase inhibitor 1 (TIMP1) and stanniocalcin 2 (STC2) expression levels in patients with gastric cancers to assess their clinical application for diagnosing and monitoring diseases. METHODS: Real-time reverse transcription-polymerase chain reaction was used to detect the expression levels of KAP1, TIMP1, STC2, talin 2 (TLN2), sushi-repeat-containing protein, X-linked 2 (SRPX2) and secreted protein, acidic, cysteine-rich (SPARC) in the patients' peripheral blood karyocytes. The data were analyzed with receiver operating characteristics (ROC) curves. RESULTS: A total of 112 patients with gastric cancer, 42 patients with recurrence and 107 healthy volunteers were recruited. There were significant correlations between KAP1, TIMP1 and STC2 levels, and TNM tumor stages and distant metastases. The area under the ROC curves (AUC) of KAP1 was 0.803 ± 0.040 (P = 0.0001), the AUC of TIMP1 was 0.767 ± 0.043 (P = 0.0001) and the AUC of STC2 was 0.769 ± 0.045 (P = 0.0001), thus differentiating preoperative gastric cancer patients from healthy volunteers by ROC curve analysis. The AUC of STC2 was 0.739 ± 0.070 (P = 0.004) and the AUC of KAP1 was 0.418 ± 0.088 (P = 0.319), thus differentiating recurrence of gastric cancer from healthy volunteers by ROC curve analysis. High TIMP1 and STC2 expression levels were suspected to be poor prognostic factors of disease recurrence in patients with gastric cancer. CONCLUSIONS: KAP1, TIMP1 and STC2 expression levels may be potential biomarkers for the screening, diagnosis, prognosis and surveillance of gastric cancer.

Clinicopathologic significance of miR-10b expression in gastric carcinoma.

We have investigated microRNA (miRNA) expression profiles of gastric cancer and the clinicopathologic significance of miR-10b expression in gastric carcinoma. miRCURY LNA Arrays (v.16.0; Exiqon, Vedbaek, Denmark) were used to screen miRNAs in 17 gastric cancers. Reverse transcriptase polymerase chain reaction was performed to determine the expression of miR-10b in 56 gastric tumors. Expression of miR-10b in 436 paraffin-embedded cancer tissues was also investigated. In gastric cancer, 49 miRNAs were overexpressed by 2.0-fold or greater, and 39 miRNAs were down-regulated by 1.5-fold or greater, whereas miR-10b was up-regulated by 2.98-fold. miR-10b was highly expressed in gastric cancer and correlated with size of tumor, Lauren classification, depth of invasion, lymph node and distant metastasis, TNM stage, and prognosis. In stages I, II, and III, the 5-year survival rate of patients with high levels of miR-10b expression was significantly lower than that in patients with low levels of expression. In stage IV, the expression level of miR-10b did not correlate with the 5-year survival rate. miR-10b may play an important role in progression and prognosis of gastric cancer.

L1 and epithelial cell adhesion molecules associated with gastric cancer progression and prognosis in examination of specimens from 601 patients.

BACKGROUND: L1 cell adhesion molecule (L1CAM) and epithelial cell adhesion molecule (EPCAM) have been implicated in the development and progression of gastric cancer. The present study investigated the clinical significance of L1CAM and EPCAM in the development, progression and prognosis of gastric cancer. METHODS: Expression of L1CAM and EPCAM were examined immunochemically in 601 clinicopathologically characterized gastric cancer cases. RESULTS: L1CAM protein was detected in 23.9% of human non-tumor mucosa samples. All samples expressed L1CAM protein at low levels. High expression of L1CAM protein was detected in 163 (27.1%) tumors. Expression of L1CAM correlated with age, tumor location, size of tumors, Lauren's classification, depth of invasion, lymph node and distant metastases, regional lymph node stage, Tumor-Node-Metastasis (TNM) stage and prognosis. EPCAM protein was detected in 45.7% of human non-tumor mucosa samples. All samples expressed EPCAM protein at low levels. High expression of EPCAM protein was detected in 247 (41.1%) tumors. Expression of EPCAM correlated with age, tumor location, size of tumors, Lauren's classification, depth of invasion, lymph node and distant metastases, regional lymph node stage, TNM stage and prognosis. Cumulative 5-year survival rates of patients with high expression of both L1CAM and EPCAM were significantly lower than in patients with low expression of both. CONCLUSIONS: Expression of L1CAM and EPCAM in gastric cancer was significantly associated with lymph node and distant metastasis, and poor prognosis. L1CAM and EPCAM proteins could be useful markers to predict tumor progression and prognosis.

[Association of SOX9 expression and prognosis in patients with gastric cancer].

OBJECTIVE: To investigate the association of SOX9 expression and clinicopathologic factors and prognosis of gastric cancer. METHODS: A retrospective cohort study including 112 gastric cancer patients admitted to the Zhejiang Provincial People's Hospital from 2004 to 2006 was performed. Immunohistochemical analysis was used to evaluate the expression of SOX9 in the 112 specimens of gastric cancer tissues and 70 non-cancerous tissues adjacent to the tumor. RESULTS: Low expression of SOX9 was seen in 5(7.1%) tissues out of 70 non-cancerous tissues adjacent to the tumor. A total of 94(83.9%) patients had varying expression of SOX9, of whom 51(45.4%) had overexpression. Univariate analysis demonstrated that the expression of SOX9 was significantly associated with Lauren classification (P<0.05), tumor invasion(P<0.01), lymph node metastasis(P<0.05), distant metastasis(P<0.05) and tumor stage(P<0.05), however there was no significant association between SOX9 expression and sex, age, histological type, histology differentiation or tumor size. Kaplan-Meier analysis showed that the 5-year survival rate of patients with SOX9 over-expression was significantly lower than that of patients with low expression(29.4% vs. 49.2%, P=0.031). Multivariate Cox regression analysis showed that histology differentiation(P=0.046), tumor invasion(P=0.001), and distant metastasis(P<0.01) were independent prognostic factors for gastric cancer, however the over-expression of SOX9 was not significant(P=0.948). CONCLUSIONS: The expression SOX9 is associated with the growth, invasion, and metastasis of gastric cancer, as well as the prognosis. However, SOX9 expression is not an independent factor for the prognosis in patients with gastric cancer.

Upregulated expression of ADAM17 is a prognostic marker for patients with gastric cancer.

OBJECTIVE: This study was designed to evaluate the expression and prognostic significance of A Disintegrin and Metalloproteinase17 (ADAM17) protein in patients with gastric cancer. BACKGROUND: Tumor invasion and metastasis are primary causes for treatment failure or death among cancer patients. ADAM17 is a multidomain transmembrane glycoprotein involved in the release of several ligands that were shown to promote tumor formation and progression. Elevated expression of ADAM17 was detected in a number of human cancers and was associated with poor progression and prognosis of the diseases. In gastric cancer, however, the expression and prognostic significance of ADAM17 has not been fully elucidated. METHODS: The expressions of ADAM17 and extracellular matrix metalloproteinase inducer (EMMPRIN), a protein implicated in tumor invasion and metastasis, were detected using the tissue microarray technique and immunohistochemical EnVision method and compared with clinicopathological parameters of patients with gastric cancer. RESULTS: The expressions of ADAM17 and EMMPRIN were upregulated in gastric cancer lesions compared with their expressions in adjacent non-cancerous tissues (P < 0.01). High expression of ADAM17 was detected in 35.78% (156/436) of patients with gastric cancer and positively correlated with the expression of EMMPRIN (r = 0.738, P < 0.01). ADAM17 expression was associated with a number of clinicopathological parameters including depth of invasion and TNM stage of the tumor (P < 0.05). In each TNM stage, patients with high ADAM17 expression had a longer mean survival time than those with low expression (P < 0.05). Particularly, the mean survival time of stage II gastric cancer patients with low ADAM17 expression was longer than that of stage I patients with high ADAM17 expression (P < 0.01). Multivariate survival analysis suggested that, along with other parameters, ADAM17 and EMMPRIN expression were independent prognostic factors for patients with gastric cancer. CONCLUSIONS: ADAM17 was implicated in the progression of gastric cancer. On the basis of the TNM stage, detection of ADAM17 expression will be helpful for predicting prognosis of gastric cancer.