Browsing by Subject "Gastric carcinomas"
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- PublicationOpen Accessa-Methylacyl coenzyme A racemase is highly expressed in the intestinal-type adenocarcinoma and high-grade dysplasia lesions of the stomach(Murcia : F. Hernández, 2008) Huang, Wenbin; Zhao, Jianhua; Li, Li; Huang, Yue; Yang, Xiaobin; Wang, Jinsong; Zhang, TonghaiTo study a-Methylacyl coenzyme A racemase (AMACR) expression in gastric intestinal-type adenocarcinoma and its precursors, we performed an immunohistochemical assay (using an avidin-biotinperoxidase complex method) on 106 paraffin-embedded gastric mucosal biopsy samples and 25 gastrectomy samples (37 negative for dysplasia; 30 indefinite for dysplasia; 22 low-grade dysplasia; 25 high-grade dysplasia; and 34 invasive intestinal adenocarcinoma). The results showed that AMACR staining was uniformly negative in the groups negative for dysplasia and indefinite for dysplasia. Only 1 of 22 (4.5%) low-grade dysplasia showed weak staining for AMACR. In the groups of high-grade dysplasia and invasive intestinaltype adenocarcinoma, however, 19 of 25 (76%) and 18 of 34 (52.9%) were positive for AMACR respectively. Expression of AMACR was not correlated with location, H. Pylori infection or intestinal metaplasia. These results suggested that AMACR may play a role in the intermediate stage of gastric carcinogenesis. The high level expression of AMACR in high-grade dysplasia and carcinoma suggests that it may be a useful biomarker in distinguishing high-grade dysplasia and carcinoma from low-grade dysplasia.
- PublicationOpen AccessClinicopathological significance of MMP-2 and its specific inhibitor TIMP-2 in gastric cancer(Murcia : F. Hernández, 2008) Alakus, H.; Grass, G.; Hennecken, J.K.; Bollschweiler, E.; Schulte, C.; Drebber, U.; Baldus, S.E.; Metzger, R.; Hölscher, A.H.; Mönig, S.P.Matrix metalloproteinases (MMPs) can degrade type IV collagen of extracellular matrices and basal membranes and thus play a key role in the migration of malignant cells. In vivo, MMPs are inhibited by tissue inhibitors of metalloproteinases (TIMPs). Since in a previous study we showed that the expression of MMP-2 correlates with clinicopathological parameters in gastric cancer, we have now investigated a possible correlation of MMP-2 and TIMP-2 expression with survival in gastric cancer, as well as the possible association of TIMP-2 with clinicopathological parameters. Tissue samples were obtained from 116 gastric cancer patients who underwent gastrectomy with extended lymphadenectomy. MMP-2 and TIMP-2 expression was analysed using immunohistochemical staining and was graded semiquantitatively (score 0 – 3). High epithelial MMP-2 immunoreactivity was significantly associated with tumor stage and poor survival using the Kaplan-Meier log-rank statistical method (log-rank statistics). However, using Cox regression analysis, high epithelial MMP-2 immunoreactivity was not an independent prognostic factor. TIMP-2 showed no association with survival in gastric cancer, but the intensity of TIMP-2 staining in tumor cells correlated significantly with tumor differentiation based on the WHO and Lauren and Ming classifications, as well as with presence of distant metastasis. Our results show that high epithelial MMP-2 expression in gastric cancer is associated with poor survival, although it is not an independent prognostic factor, and that aggressive forms of gastric cancer are associated with low TIMP-2 expression.
- PublicationOpen AccessEffects of Helicobacter pylori on biological characteristics of gastric epithelial cells(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2012) Wang, Ping; Mei, Juan; Tao, Jing; Zhang, Ning; Tian, Hua; Fu, Guo-HuiInfection with Helicobacter pylori (H. pylori) strains is linked to an increased risk of inflammation and gastric cancer. To investigate the effects of H. pylori on biological characteristics of gastric epithelial cells SGC-7901, derived from human adenocarcinoma, morphological appearances of both the pathogen and these cells, as well as features of attachment and internalization were observed by using transmission electron microscopy (TEM). We also investigated cell junctions and invasion by TEM and Transwell Invasion Assay. Cell proliferation and apoptosis were assessed by using chromogenic methylthiazol tetrazolium bromide (MTT) dye and flow cytometry. Three types of H. pylori were observed around, attaching to, or invading tumor cells. Cellular damage was characterized by vacuolar degeneration, dilated endoplasmic reticulum (ER), and reduction of organelles. Cell junctions and cell microvilli reduced or disappeared. H. pylori inhibited cell proliferation, whereas it had no effect on apoptosis. It also promoted gastric carcinoma cell invasion. H. pylori damages cell construction, destroys cell junctions, inhibits cell proliferation, promotes cell invasive ability, and, therefore, might accelerate the malignant progress and metastasis of gastric cancer
- PublicationOpen AccessExtensive alteration in the expression profiles of TGFB pathway signaling components and TP53 is observed(Murcia : F. Hernández, 2008) Seok-Hyung Kim; Seung-Hyun Lee; Yoon-La Choi; Li-Hui Wang; Cheol Keun Park; Young Kee ShinSummary. Aims: The expression patterns of TGFB signaling proteins, such as TGFB1/2, TGFBR1(ALK5), TGFBR2, SMAD1/2/3, SMAD2/3, SMAD4, SMAD7, and of downstream targets of TGFB signaling, CDKN1A (p21CIP1), CDKN1B (p27KIP1), MYC, CDC25A, TP53, and RELA (p65NF-kB) were investigated in gastric carcinomas and other gastric lesions. Methods and results: A total of 112 gastric carcinomas, 37 dysplasias, 54 intestinal metaplasias, 29 chronic atrophic gastritis and 54 normal gastric epithelium were analyzed by tissue microarray-based immunohistochemical analysis. Extensive changes in expression profiles of these proteins were observed. Three types of expression patterns were observed along the normal epithelium-atrophic gastritis-dysplasiacarcinoma sequence. (1) Expression of TGFB1/2, TGFBR1, MYC, and TP53 continually increased along this sequence. (2) Expression of SMAD4, CDKN1A, SMAD1/2/3, SMAD2/3, and CDKN1B was enhanced in dysplasia but decreased in carcinoma. (3) Expression of TGFBR2, SMAD7, RELA, and CDC25A was enhanced in dysplasia and the enhanced level was maintained in carcinoma. In addition, we also evaluated the clinical significance of the expression of TGFB signaling proteins in gastric carcinoma. TGFB and MYC were positively correlated with advanced stages, whereas SMAD1/2/3 and SMAD4 were strongly associated with earlier stages. Conclusions: The extensive change in expression of TGFB signaling components is implicated during tumorigenesis of gastric neoplasias.
- PublicationOpen AccessImmunohistochemical detection of cell proliferation in gastric carcinomas with the monoclonal antibody ki-67. A study of 24 cases(Murcia : F. Hernández, 1993) Hoang, Catherine; Polivka, Marc; Maragi, J.A.; Valleu, P.; Nemeth, J.; Galian, AnnieThe proliferative activity in 24 gastric carcinomas was determined by an immunohistochemical method using monoclonal antibody Ki-67 (ABC method). Immunostained nuclei were counted by two observers through a Nachet NS 1000 image numeriser. Three grades were defined according to stained nuclei percentage (proliferation index Pi = percentage of cells engaged in cellular cycle outside Go): grade 1 (Pi < 20%); grade 2 (20% < Pi < 40%); grade 3 (Pi > 40%). About 60% of tumours were in grade 1 and 10% in grade 3. No correlations were observed between Pi and the following parameters: histological differentiation; parietal extension; presence or absence of metastasis. These results may be compared to the two other avalable studies of Ki-67 antibody in gastric cancers. Our study also showed a heterogeneous distribution of immunostained nuclei, within each single tumour and from one tumour to another, which has been noted in one previous study and in a similar one we made on colorectal carcinoma. This heterogeneity is the consequence of the variability of carcinomatous cell proliferative activity; an important biological factor in the evaluation of tumoral process. The proliferative activity in gastric carcinomas provides an estimation of tumour dynamics that might be a prospective criterium for tumoral process evaluation.
- PublicationOpen AccessMinute and small early gastric carcinoma with special reference to eosinophil infiltration(Murcia : F. Hernández, 1993) Caruso, R.A.; Giuffre, G.; Inferrera, C.The authors examined 25 minute early gastric cancers (EGC) and 13 small EGC in order to investigate the incidence and possible causes for the infiltration of eosinophils. The degree of eosinophil infiltration was higher in tumour stroma than in adjacent normal-appearing mucosa; this correlation was statistically significant (P < 0.001). Tumour-associated tissue eosinophilia (TATE) was not correlated with size, histological type, necrosis of the tumour nor gastritis activity in adjacent non-tumoral mucosa. Electron microscopy, performed in 4 cases of small EGC, showed tumour stromal eosinophils with morphological evidence of activation similar to those described for tissue eosinophils in various disorders. Some tumour cells in intimate contact with activated eosinophils exhibited foca1 cytopathic changes. TATE represents local inflammation probably leading to tumour cell damage. The immunological role of the eosinophils against tumour cells in vivo deserves further investigation.
- PublicationOpen AccessThe pathobiological behaviors and prognosis associated with Japanese gastric adenocarcinomas of pure WHO histological subtypes(Murcia : F. Hernández, 2010) Zheng, Hua-Chuan; Zheng, Yu-shuang; Xia, Pu; Xu, Xiao-yan; Xing, Ya-nan; Takahashi, Hiroyuki; Guan, Yi-Fu; Takano, YasuoJapan is a high-risk region for gastric carcinoma with a comparatively early stage and favorable prognosis. To clarify the pathobiological behaviors and prognosis of Japanese gastric adenocarcinoma, we analyzed the clinicopathological characteristics of different WHO subtypes of carcinomas. The expression of ki-67, CPP32, p53, FHIT, maspin, parafibromin, GRP78, GRP94, EMMPRIN, VEGF, P-GSK3ß-ser9, fascin, cortactin, Arp2, Arp3 MUC-2, MUC-5AC and MUC-6 was examined using immunohistochemistry and tissue microarrays. The majority of cases were well-, poorly-, or moderatelydifferentiated subtype, whereas the minority were papillary or signet ring cell carcinoma (SRC). Patients with poorly-differentiated or SRC carcinoma were predominantly young and female. Poorly-differentiated and mucinous carcinomas were larger, with deeper invasion, more venous or lymphatic invasion, frequent lymph node involvement and peritoneal dissemination, or higher staging. The SRC group exhibited weaker expression of ki-67, CPP32, p53, parafibromin, GRP78, GRP94, P-GSK3ß-ser9, VEGF or cortactin. The moderately-differentiated subtype exhibited lower expression of FHIT and Arp3 positivity. The poorlydifferentiated group showed weaker expression of CPP32, EMMPRIN, MUC-2, MUC-5AC, and MUC-6. Survival analysis indicated that the patients with poorlydifferentiated or mucinous subtypes had a lower cumulative survival rate than those with papillary, well-, moderately-differentiated, or SRC carcinomas (P<0.05). The age, invasive depth, lymphatic invasion, peritoneal dissemination, and WHO classification were independent prognostic factors for carcinoma patients (P<0.05). It was suggested that poorly-differentiated and mucinous subtypes are more aggressive and of unfavorable prognosis among Japanese gastric carcinomas. Lower levels of proliferation and apoptosis, as well as alterations in tumor suppressor genes, mucin production and ER stress protein played important roles in the pathogenesis of poorly-differentiated and SRC carcinomas.
- PublicationOpen AccessUp-regulated expression of Ezrin and c-Met proteins are related to the metastasis and prognosis of gastric carcinomas(F. Hernández y J.F. Madrid. Murcia: Universidad de Murcia, Departamento de Biología Celular e Histología., 2011) Zhao, Jing; Zhang, Xiaoxiao; Xin, YangRecent publications demonstrated that abnormal expression of Ezrin and c-Met proteins were related to carcinogenesis, metastasis and prognosis of various sorts of tumors. In this study we detected the expressions of Ezrin and c-Met proteins in normal gastric mucosa, chronic atrophic gastritis, intestinal metaplasia, dysplasia and gastric carcinoma and analyzed the correlations with metastasis and prognosis of gastric carcinomas. The results demonstrated that both Ezrin and c-Met overexpression were related to the occurrence and progression of gastric carcinoma. Our findings also demonstrated that combined detection of these two tumor-specific biomarkers in gastric carcinomas can provide additional efficacy in predicting the patients’ outcomes.