Clonality analysis of synchronous gastro-oesophageal junction carcinoma and distal gastric cancer by whole-exome sequencing.

Gastro-oesophageal junction (GEJ) carcinoma and distal gastric cancer (GC) have distinct epidemiology and clinical features and their relationship is uncertain. Synchronous multiple gastric cancers located mostly at proximal and distal sites provide rare specimens for investigating the comprehensive genomic relationships among these cancers in the context of identical genetic circumstances. Formalin-fixed, paraffin-embedded (FFPE) samples from 12 patients with synchronous GEJ carcinoma and distal GC were collected in this study. Whole-exome sequencing (WES) was performed using normal tissues as a control. Mutational profiling, clonality analysis, a detailed clinico-pathological review, determination of MSI status, EBER in situ hybridization (ISH), and programmed cell death 1 (PD-1)/programmed death-ligand 1 (PD-L1) immunohistochemical staining were performed. Twenty-three of the 24 samples were microsatellite-stable (MSS). Subclonal analysis revealed that nine pairs of GEJ and distal GC tumours in neoadjuvant chemotherapy naïve patients developed independently from different origins. Two patients who received neoadjuvant chemotherapy shared clonal origins with highly similar somatic alterations. The remaining one patient who shared a rare mutation died within 6.2 months at the N3 stage. However, the enriched pathway identified from the overall mutation spectra in distal GC and GEJ carcinoma showed the close relationship of these cancers. Thus, although these cancers may have similar characteristics, histopathological and genetic profiling from single tumour specimens may still underestimate the mutational burden and somatic heterogeneity of multiple GCs. In addition, this series of cases also showed a PD-L1 expression rate of 58.3% and 66.7% in distal GC and GEJ carcinoma, respectively, with all the cases expressing PD-1. This result suggests the potential benefit of immunotherapeutic treatments. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

[Expression of CCAAT/enhancer binding protein beta in human gastric carcinoma and its clinical significance].

OBJECTIVE: To explore the expression of CCAAT/enhancer binding protein beta (CEBPB) in gastric carcinoma tissues and its association with clinicopathological features and prognosis. METHODS: CEBPB protein expression level was detected by immunohistochemistry method in resected gastric carcinomas and adjacent gastric mucosa tissues (n=81), and its association with clinicopathological features and prognosis was analyzed. RESULTS: The immunohistochemical staining of CEBPB was predominantly in the nucleus with some cytoplasmic staining. As a result, 16% (13/81) of the gastric carcinomas were stained positively, whereas there was hardly positive expression in adjacent gastric mucosa tissues. There was a significant association between the expression of CEBPB and distant metastasis on univariate analysis (P<0.05). The median survival time in patients with positive CEBPB expression was significantly lower than those with negative CEBPB expression (19.4 months vs. 45.2 months, P=0.024). Multivariable analysis showed that CEBPB was independently associated with prognosis (HR=2.544, 95%CI:1.154-5.610, P=0.021). CONCLUSION: Up-regulation of CEBPB suggests poor prognosis in patients with gastric cancer.

Presence of S100A9-positive inflammatory cells in cancer tissues correlates with an early stage cancer and a better prognosis in patients with gastric cancer.

BACKGROUND: S100A9 was originally discovered as a factor secreted by inflammatory cells. Recently, S100A9 was found to be associated with several human malignancies. The purpose of this study is to investigate S100A9 expression in gastric cancer and explore its role in cancer progression. METHODS: S100A9 expression in gastric tissue samples from 177 gastric cancer patients was assessed by immunohistochemistry. The expression of its dimerization partner S100A8 and the S100A8/A9 heterodimer were also assessed by the same method. The effect of exogenous S100A9 on motility of gastric cancer cells AGS and BGC-823 was then investigated. RESULTS: S100A9 was specifically expressed by inflammatory cells such as macrophages and neutrophils in human gastric cancer and gastritis tissues. Statistical analysis showed that a high S100A9 cell count (> = 200) per 200x magnification microscopic field in cancer tissues was predictive of early stage gastric cancer. High S100A9-positive cell count was negatively correlated with lymph node metastasis (P = 0.009) and tumor invasion (P = 0.011). S100A9 was identified as an independent prognostic predictor of overall survival of patients with gastric cancer (P = 0.04). Patients with high S100A9 cell count were with favorable prognosis (P = 0.021). Further investigation found that S100A8 distribution in human gastric cancer tissues was similar to S100A9. However, the number of S100A8-positive cells did not positively correlate with patient survival. The inflammatory cells infiltrating cancer were S100A8/A9 negative, while those in gastritis were positive. Furthermore, exogenous S100A9 protein inhibited migration and invasion of gastric cancer cells. CONCLUSIONS: Our results suggested S100A9-positive inflammatory cells in gastric cancer tissues are associated with early stage of gastric cancer and good prognosis.

PTK7 as a novel marker for favorable gastric cancer patient survival.

BACKGROUND AND OBJECTIVES: Protein tyrosine kinase 7 (PTK7) plays important functions in several cancer types but its expression in gastric cancer remains unknown. This study was designed to investigate PTK7 expression in gastric cancer. METHODS: PTK7 expression was assessed by immunohistochemistry in 201 gastric cancer patients. The relationship between PTK7 expression and clinicopathological features and patients prognosis were statistically analyzed. RESULTS: PTK7 expression was detected in 56.72% (114 of 201) of gastric cancer patients. The immunostaining was predominantly localized in the cytoplasm. The statistical analyses showed that PTK7 expression was more frequently detected in patients with well-differentiated tumors (P = 0.001). Furthermore, PTK7 expression was significantly related to the favorable overall survival (OS; P = 0.012) and disease-free survival (DFS; P = 0.009). Multivariate Cox regression analyses revealed that PTK7 expression was an independent prognostic factor for both favorable OS (P = 0.028) and DFS (P = 0.012). CONCLUSION: Our findings demonstrate that PTK7 can serve as a novel prognostic biomarker for gastric cancer patients.

[Clinical value of serum CEA, CA19-9, CA72-4 and CA242 in the diagnosis and prognosis of gastric cancer].

OBJECTIVE: To investigate the clinical value of tumor markers CEA, CA19-9, CA72-4 and CA242 in the diagnosis and prognosis of patients with gastric cancer. METHODS: One hundred and sixty gastric cancer patients who had received treatment from 2002 to 2007 at the Beijing Cancer Hospital were retrospectively analyzed. Blood samples were taken from patients upon admission to the hospital, and CEA, CA19-9, CA72-4, CA242 levels were detected. Statistical analysis was performed to identify the clinical value of these tumor markers in diagnosis and prognosis. RESULTS: On initial diagnosis, the positive rates of CEA, CA19-9, CA72-4 and CA242 were 37.7%, 26.7%, 37.6% and 21.3%, respectively, and the positive rate of combined detection was 62.9%. CEA was more frequently positive in patients with lymph node metastasis (P=0.029); CA72-4 was more frequently positive in patients with vascular involvement and advanced stage (P=0.039, P=0.011). Multivaraite analysis showed that CA72-4 was an independent prognostic factor (P=0.012). Patients with positive CA72-4 carried a 2.147-fold increased risk of death than those with negative CA72-4. Kaplan-Meier analysis showed that patients with positive CA19-9 or positive CA72-4 had worse survival than those with negative CA19-9 or CA72-4 (P=0.006, P=0.002). CONCLUSIONS: Tumor markers including CEA, CA19-9, CA72-4 and CA242 have clinical significance and prognostic value in patients with gastric cancer. Combined detection of four tumor markers can increase the positive rate. CA72-4 is an independent prognostic factor. CA19-9 and CA72-4 are associated with the prognosis of patients with gastric cancer.

Survival stratification panel of colorectal carcinoma with combined expression of carcinoembryonic antigen, matrix metalloproteinases-2, and p27 kip1.

PURPOSE: The prognosis varies greatly in colorectal carcinoma patients, even in the same stage. We examined the association between the expression of matrix metalloproteinases-2, carcinoembryonic antigen, p27 kip1, and clinicopathologic features in patients with colorectal carcinoma to identify a possible panel of tumor markers in predicting prognosis of colorectal carcinoma. METHODS: The expressions of three individual markers in 127 colorectal carcinoma cases were analyzed by immunohistochemistry method. Univariate and multivariate analysis were performed to analyze the expression with the disease-free survival time in colorectal carcinoma. RESULTS: High expression of matrix metalloproteinases-2, carcinoembryonic antigen, and low expression of p27 kip1 were related to poor prognosis in univariate analysis (P = 0.0002; P < 0.0001; P = 0.0008). The expression of matrix metalloproteinases-2, carcinoembryonic antigen, p27 kip1, and tumor differentiation were independent prognostic factors for disease-free survival by Cox regression analysis. The coexpression panel of matrix metalloproteinases-2, carcinoembryonic antigen, and p27 kip had significant prognostic value in all patients (P AB = 0.0103; P(BC) = 0.0068; P CD = 0.0117). Multivariate analysis with Cox regression reveals that coexpression of matrix metalloproteinases-2, carcinoembryonic antigen, and p27 kip1 were independent prognostic factors as tumor differentiation in colorectal carcinoma. In different stages, coexpression tumor markers functioned in Stages II and III but not in the 19 cases of Stage I. The reason might be the number of patients was too small. CONCLUSIONS: The results of this study provided further evidence that the combination of tumor markers of matrix metalloproteinases-2, carcinoembryonic antigen, and p27 kip1 was more informative than any single tumor marker alone for the disease-free survival stratification of colorectal carcinoma. Coexpression of matrix metalloproteinases-2, carcinoembryonic antigen, and p27 kip1 might be a useful survival stratification panel for clinical management.

[Ultraviolet transmission spectra of BC(x)N thin films].

BCN, BC2N and BC3N thin films with transmission increasing properties in the ultraviolet region were deposited by RF magnetron sputtering with different sputtering power (80-130 W). Fourier transform infrared absorption and X-ray photoelectron spectroscopy results suggested that the films were atomnic-level hybrids composed of B, 'C and N atoms. The compositions and transmission increasing properties of samples in the ultraviolet region were strongly influenced by sputtering power, which determined the transmission increasing properties in the ultraviolet region by changing compositions. And the lower the atomic number of C in the thin films, the better the transmission increasing properties in the ultraviolet region. The BCN thin films deposited at the sputtering power of 110 W possessed the lowest atonic number of C and the best transmission increasing properties in the ultraviolet region. And the increase in average transmissivity from 200 to 350 nm was about 40% compared with glass.

Compatibility of tissue conditioners and dental stones: effect on surface roughness.

STATEMENT OF PROBLEM: Although the primary use of tissue conditioners is to treat abused mucosa, these materials are also frequently used as functional impression materials. No information was identified on the effect that these materials may have on the surface of the resultant dental stone cast. PURPOSE: This study evaluated the compatibility of 3 tissue conditioners with dental stones and changes in surface conditions over time. MATERIAL AND METHODS: Three tissue conditioners (COE-comfort, Soft-conditioner, and Visco-gel) and 4 dental stones (Capstone DF, New Plastone, Die Stone, and New Fujirock) were evaluated. One impression material (Examixfine) was used as a control. Tissue conditioner disks were made by pouring freshly mixed material into a polypropylene container, pressing the material down with a glass plate, and then removing the plate 2 hours later. The disks were then stored in distilled water for 0 or 24 hours, or 3, 7, or 14 days. Subsequently, each dental stone was mixed and poured over the top of each disk and allowed to remain for 60 minutes. Twenty-five disk-shaped specimens, 18 x 2 mm, for each tissue conditioner/stone cast combination were prepared. Mean surface roughness (Ra) values of the dental stone casts made from the tissue conditioners were determined using a profilometer. Five measurements for each specimen were made. Data were analyzed with 1- and 3-way analysis of variance and the Student-Newman-Keuls test (alpha=.05). Detail reproduction was also determined using a ruled test block, as specified in ISO specification 4823. RESULTS: Contribution ratios determined by 3-way analysis of variance indicated that the surface roughness values were significantly more influenced by the time of immersion in water ( P <.0005, contribution ratio rho=37%), than the type of tissue conditioner ( P <.0005, rho=19%) or dental stone used ( P <.0005, rho=1%). The best surface quality was obtained with a New Fujirock cast (0.81 +/- 0.06 microm), followed by New Plastone (0.83 +/- 0.12 microm) and Die Stone (0.85 +/- 0.05 microm) casts, in combination with Visco-gel without immersion in water, and those were nearly equivalent in surface roughness to a Die stone cast from Examixfine. The surface roughness values of all specimens, especially the COE-comfort/stone cast combinations, significantly increased with tissue conditioner immersion time ( P <.0005). Visco-gel tended to produce a better surface quality during the test periods than the other materials. All stone casts made from the tissue conditioners not immersed in water reproduced 20-microm or 50-microm lines, while the detail diminished over time with immersion. CONCLUSION: The type of tissue conditioner, and especially immersion time, had a significant effect on the surface quality of dental stone casts. The type of dental stone used is less important.