Che Xiangming

Clinical impact of intratumoral natural killer cell and dendritic cell infiltration in gastric cancer.

Intratumoral natural killer cells (NKC) and dendritic cells (DC) may affect the clinical features of various gastrointestinal cancers. However, the relationship between intratumoral NKC and DC remains unclear. We examined 169 patients with gastric cancer who underwent gastrectomy at Kagoshima University Hospital. Immunohistochemical staining of CD57 and S-100-protein was performed to evaluate NKC and DC infiltration, respectively. A total of 25 areas containing pericancerous tissue were selected for determining the number of NKC and DC under high power microscopy (x400). Patients were classified into two groups according to NKC and DC population. Intratumoral lymphocytic infiltration was also calculated in 15 areas with a high power (x400) objective. The degree of NKC and DC infiltration was gradually decreased according to the progression of nodal involvement. Patients with many NKC infiltration had a lower positivity of lymph node metastasis and lymphatic invasion than patients with little NKC infiltration. DC infiltration was also negatively correlated with depth of invasion, lymph node metastasis and curativity. DC infiltration was positively correlated with lymphocytic infiltration (P=0.01. r=0.6). The 5-year survival rates of patients with many NKC infiltration and patients with DC many infiltration were 75 and 78%, respectively, both of which were significantly better than that of patients with little NKC and DC infiltration (P<0.05). NKC may be activated without DC or intratumoral lymphocytes. Intratumoral NKC may act as an independent immunologic effector against tumor cells, unlike DC.

Angiogenesis as an unfavorable factor related to lymph node metastasis in early gastric cancer.

AbstractBackground: Recent studies suggest that angiogenesis enhances tumor growth and metastasis. Lymph node metastasis influences the prognosis and selection of treatment modalities in cancers. In this study, the authors investigated the correlation between angiogenesis and clinicopathologic features to determine whether angiogenesis correlated with lymph node metastasis in early-stage gastric cancer. Methods: A total of 97 specimens from patients with early gastric cancer were studied by immunohistochemical methods using anti-Factor VIII-related antigen antibody. Results: Tumor size was significantly correlated with microvessel count, which increased as tumor size increased. Microvessel counts from tumors with lymphatic vessel invasion, lymph node metastasis, and submucosal invasion were significantly higher than those without. Furthermore, microvessel count was an independent factor that influenced lymph node metastasis (P=.0016) by multivariate logistic regression analysis. Conclusion: In the early stage of gastric carcinoma, angiogenesis is an independent factor that impacts on lymph node metastasis.

Cooccurrence of Reduced Expression of α-Catenin and Overexpression of p53 Is a Predictor of Lymph Node Metastasis in Early Gastric Cancer

Background and Objectives: Even though the pathological background contributes to lymph node metastasis, the biological characteristics of tumors have also gained wide attention. In this study, the expression of the cadherin-catenin complex and p53 was studied in early gastric cancer. Their correlation with lymph node metastasis and the predictability of lymph node metastases, by combining these factors, were also discussed. Methods: One hundred and one specimens obtained from surgery were studied by immunohistochemistry using monoclonal anti-E-cadherin, anti-α-catenin and anti-p53 antibodies. Results: Expression of E-cadherin and α-catenin was reduced in 50.5 and 64.4%, respectively. p53 protein staining was positive in 29.7%. There was a significant correlation between E-cadherin and α-catenin expression, but no correlation was found between p53 expression and E-cadherin or α-catenin expression. A reduction in α-catenin expression and p53 overexpression correlated to lymph node metastases, respectively. Multivariate analysis showed that cooccurrence of reduced expression of α-catenin and overexpression of p53 was an independent factor indicating lymph node metastases. Conclusion: A study of both α-catenin and p53 expression may be helpful to predict lymph node metastases in early gastric cancer.

p21 expression is a prognostic factor in patients with p53-negative gastric cancer

The expression of p21 and p53 proteins was analyzed by immunohistochemistry in 256 patients with advanced gastric cancer. The results showed that strong, weak and negative expression of p21 were detected in 22.2 (57/256), 68.0 (174/256) and 9.8% (25/256) of the patients, respectively. p53 expression was found in 28.9% (74/256). The expression of p21 was not associated with clinicopathological features. In p53 negative tumors, p21 expression was associated with the survival of patients who underwent curative operations (P = 0.007). The 5-year survival rates were 20.1, 36.6 and 59.8% in patients with p21-negative, -weakly positive and -strongly positive tumors, respectively. In contrast, in p53-positive tumors, prognosis did not differ in spite of p21 expression. Multivariate analysis showed that p21 expression was an independent factor in patients with p53-negative tumors. These results indicate that examination of p21 expression in p53 negative tumors will be useful for estimating the prognosis of patients with advanced gastric cancer.

Role of cyclin E and p53 expression in progression of early gastric cancer

Background. To elucidate the role that cyclin E overexpression plays in the progression of early gastric cancer, we examined the expression of cyclin E and p53, as abnormal p53 expression is linked with cyclin E overexpression in exerting adverse affects on the cell cycle. Methods. Specimens from 108 early gastric cancers were stained by an immunohistochemical method, using anti-cyclin E and anti-p53 antibodies. Results. The positivity rate of cyclin E expression in early gastric cancer was 33% (36/108). Cyclin E-positive tumors invaded more deeply (P < 0.05), infiltrated lymphatic vessels more frequently (P < 0.01), showed a higher incidence of differentiated cancer (P < 0.01), and more often expressed p53 (P < 0.01) than cyclin E-negative tumors. Differentiated cancers showing coexpression of cyclin E and p53 were more likely to metastasize to the lymph nodes. Conclusions. Overexpression of cyclin E may promote the progression of early gastric cancer.

The expression of cadherin-catenin complex in association with the clinicopathologic features of early gastric cancer.

Although impaired expression of E-cadherin (E-cad) is frequently observed in tumors with aggressive histopathologic characteristics, the correlation between α-catenin (α-cat) expression and the clinicopathologic features of early gastric cancer have not been fully examined. In this study, we evaluated the expression of E-cad and α-cat by early gastric carcinomas, and examined the relationships between this expression and various clinicopathologic characteristics. A total of 69 specimens obtained from surgery were studied by immunohistochemistry. Reduced expression of E-cad and α-cat were found in 53.6% and 65.2% of the tumors, respectively, and a significant correlation was observed between the decreased expression of E-cad or α-cat and tumor histology, the quantity of stroma, and the infiltration pattern of the tumor. The reduced expression of α-cat correlated more strongly with these features than E-cadherin expression. Furthermore, α-cat expression was also related to the lymph node metastasis of tumors. The expression of E-cad or α-cat in the primary tumor was consistent with the expression of tumor cells that invaded the lymphatic vessels, but discordant with staining in the metastasized lymph nodes. In some cases, as the tumor invaded deeper, the expression of E-cad or α-cat changed from preserved to reduced. Our observations suggest that the reduced expression of E-cad or α-cat may be involved in the initial steps leading to the invasion and metastasis of early gastric cancer.

Abnormal expression of β- and γ-catenins in early gastric cancer

BackgroundE-cadherin and α-catenin are closely correlated with the clinicopathology of advanced gastric cancer, but little is known about the functions and mechanisms of β- and γ-catenins. In this study, we evaluated the expression of β- and γ-catenins in early gastric cancer.MethodsSixty-nine specimens, obtained by surgery from patients with early gastric cancer, were studied by immunohistochemistry, using monoclonal anti-β- and anti-γ-catenin antibodies.ResultsReduced expression of β- and γ-catenins was found in 28% and 39% of early gastric cancer specimens, respectively. The reduction in the expression of β-catenin was related to patient age and tumor size, while the reduction in γ-catenin expression was related to the histologic type and infiltration pattern of the tumor. A significant correlation was observed between the expression of β-catenin and that of γ-catenin. Tumors in which simultaneous staining showed heterogenous expression of β- and γ-catenins had a higher rate of lymph node metastasis.ConclusionsChanges in the quantity of β- or γ-catenin act as factors that take part in some process that indirectly affects cell-to-cell adhesion and detachment. Combined examination of β- and γ-catenins may be helpful in predicting the outcome for patients with early gastric cancer.

Expression of P21WAF1/CIP1 in the P53-dependent pathway is related to prognosis in patients with advanced esohageal cancer

The proteins p53 and p21 are important components that regulate G1-S transition through the cell cycle. We immunohistochemically investigated p53 and p21 expression in 111 patients with esophageal squamous cell carcinoma. We also evaluated whether the expression of either of these proteins is a prognostic factor according to the p53-dependent and -independent pathways. The positive rates of p53 and p21 expression were 42.8 and 43.2%, respectively. Clinicopathological findings according to p53 and p21 expression did not differ significantly. The 5-year-survival rates between p21 positive and negative expression did not differ significantly in the p53-positive group. In the p53-negative group, the 5-year-survival rate of patients with p21-positive expression was 22.9%, which was significantly better than that of patients with p21-negative expression (12.7%; P<0.05). Multivariate analysis revealed that p21 expression in the p53-dependent pathway was an independent prognostic factor. Accordingly, the prognostic values of p21 expression between the p53-dependent and -independent pathways differed. Examination of p21-positive expression in the p53-dependent pathway will help to estimate the favorable prognosis of patients with advanced esophageal carcinoma.