Arp2/3 overexpression contributed to pathogenesis, growth and invasion of gastric carcinoma.

BACKGROUND: Tumor metastasis depends on cell adhesion, motility and deformability, resulting from quantitative alterations and rearrangement of actin-related protein (Arp) 2 and 3. The aim of this study was to clarify the roles of both molecules in tumorigenesis and progression of gastric carcinomas. PATIENTS AND METHODS: Immunohistochemistry (IHC) was employed on tissue microarray containing gastric carcinomas, adjacent metaplasia and gastritis using antibodies against Arp2 and Arp3 with a comparison of their expression with clinicopathological parameters of carcinomas. Gastric carcinoma cell lines (MKN28, AGS, MKN45, KATO-III and HGC-27) were studied for Arp2 and Arp3 protein by IHC. RESULTS: Both proteins were expressed at low levels in gastritis compared with carcinomas (p < 0.05). Arp2 was more frequently expressed in intestinal metaplasia than in carcinoma and gastritis (p < 0.05). Most gastric carcinoma cell lines showed expression at different levels. Expression was positively correlated with tumor size, depth of invasion, venous invasion, Union Internationale Contre le Cancer (UICC) staging and expression of cortactin or fascin (p < 0.05), but not with age, sex, lymphatic invasion or lymph node metastasis (p > 0.05). There was stronger positivity of Arp3 in intestinal- than diffuse-type carcinomas (p < 0.05). A positive relationship between Arp2 and Arp3 proteins was noted (p < 0.05). Univariate analysis indicated that the cumulative survival rate of patients with positive Arp2 or Arp3 expression was not different from those without their expression (p > 0.05). Multivariate analysis showed that age, depth of invasion, lymphatic invasion, lymph node metastasis, UICC staging and Lauren's classification were independent prognostic factors for carcinomas (p < 0.05). CONCLUSION: Aberrant expression of Arp2 and Arp3 is possibly involved in pathogenesis, growth, invasion and progression of gastric carcinomas. Distinct Arp3 expression underlies the molecular mechanisms for the differentiation of intestinal- and diffuse-type carcinomas. They were considered as objective and effective markers to indicate the pathobiological behaviors of gastric carcinomas.

JC virus existence in Chinese gastrointestinal carcinomas.

The John Cunningham virus (JCV) infects a large proportion of the population worldwide and may cause progressive multifocal leukoencephalopathy upon immunodeficiency. Recent reports provided evidence of its oncogenetic role in malignancies. In this study, JCV was examined by targeting T antigen, viral protein and agnoprotein in paraffin-embedded or frozen gastrointestinal carcinomas and paired non-neoplastic mucosa (NNM) samples by nested-PCR followed by Southern blot analysis. In addition, the expression of JCV T antigen, ki-67, caspase-3, p53, Rb and ß-catenin was studied by immunohistochemistry on tissue microarrays. The positive rate of JCV T antigen was higher in paraffin-embedded gastrointestinal carcinomas compared to adjacent NNM by nested-PCR followed by Southern blot analysis (36.9 vs. 16.9%, P<0.05), while there was no difference in other viral oncogenes regardless of whether they were paraffin-embedded or frozen samples. Immunohistochemically, T antigen was detectable in 9.6% (13/135) of carcinoma cases, which was higher than its positive rate in NNM (0.8%, 1/126, P<0.01). However, the genomic JCV DNA existence or its T antigen expression was not correlated with age, gender, tumor size, histological types, lymph node metastasis, expression of ki-67, caspase-3, p53, Rb and ß-catenin of gastric carcinomas (P>0.05). In conlusion, JCV T antigen may be involved in gastrointestinal carcinogenesis as an oncogene in China.

The pathobiological behaviors and prognosis associated with Japanese gastric adenocarcinomas of pure WHO histological subtypes.

Japan 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-GSK3beta-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 moderately-differentiated 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-GSK3beta-ser9, VEGF or cortactin. The moderately-differentiated subtype exhibited lower expression of FHIT and Arp3 positivity. The poorly-differentiated group showed weaker expression of CPP32, EMMPRIN, MUC-2, MUC-5AC, and MUC-6. Survival analysis indicated that the patients with poorly-differentiated 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.