Diabetes-resistant NOR mice are more severely affected by streptozotocin compared to the diabetes-prone NOD mice: correlations with liver and kidney GLUT2 expressions.

Nonobese diabetic (NOD) mice are susceptible strains for Type 1 diabetes development, and Nonobese Diabetes-Resistant (NOR) mice are defined as suitable controls for NOD mice in non-MHC-related research. Diabetes is often accelerated in NOD mice via Streptozotocin (STZ). STZ is taken inside cells via GLUT2 transmembrane carrier proteins, the major glucose transporter isoforms in pancreatic beta cells, liver, kidneys, and the small intestine. We observed severe adverse effects in NOR mice treated with STZ compared to NOD mice that were made diabetic with a similar dose. We suggested that the underlying mechanism could be differential GLUT2 expressions in pancreatic beta cells, yet immunofluorescent and immunohistochemical studies revealed similar GLUT2 expression levels. We also detected GLUT2 expression profiles in NOD and NOR hepatic and renal tissues by western blot analysis and observed considerably higher GLUT2 expression levels in liver and kidney tissues of NOR mice. Although beta cell GLUT2 expression levels are frequently evaluated as a marker predicting STZ sensitivity in animal models, we report here very different diabetic responses to STZ in two different animal strains, in spite of similar initial GLUT2 expressions in beta cells. Furthermore, use of NOR mice in STZ-mediated experimental diabetes settings should be considered accordingly.

Hepatocyte antigen expression in subtypes of intestinal metaplasia of the stomach.

OBJECTIVE: Recently, hepatocyte antigen (Hep) was introduced as a sensitive and reliable marker of intestinal metaplasia (IM). However, the distribution of Hep expression in subtypes of IM was not described. METHODS: We examined the expression of Hep in 58 cases of chronic gastritis associated with IM by immunohistochemical staining. Cases were classified as: 19 of IM Type I (complete) cases, 16 cases of IM Type II (incomplete) and 23 cases of IM Type III (incomplete). The distribution of Hep expression was classified into four groups according to the intensity of Hep expressing metaplastic cells: negative, low, moderate and high. We also compared expression of Hep with that of MUC-1, MUC-2 and MUC-5AC. RESULTS: Hep expression showed granular cytoplasmic staining and was specifically identified in columnar cells, but not in goblet cells. There was no significant difference between Hep expression and subtypes of IM (p > 0.005). However the difference between the distribution of Hep expression among three subtypes of IM was significant (p < 0.001). No relationship was observed among the expression of Hep, MUC-1, MUC-2 and MUC-5AC. CONCLUSION: Results of the present study revealed that the distribution of Hep expression is high in the majority of the complete type (Type I) IM cases, moderate in the majority of the incomplete Type II IM cases and low in all of the incomplete Type III IM cases and suggest that besides its role as a sensitive marker in IM, the evaluation of the distribution of Hep expression might be useful in the classification of IM.

The prognostic relevance of angiogenesis and mast cells in squamous cell carcinoma of the oesophagus.

AIMS: Angiogenesis, an important prognostic factor in several tumours, is a complex event mediated by angiogenic factors released from cancer cells and host immune cells. Among the host immune cells, a role has been implicated for mast cells in tumour progression via promoting angiogenesis. Data have been recorded that indicate a correlation between intratumoral neovascularisation, as assessed by microvessel density (MVD), and prognosis in squamous cell carcinoma (SCC) of the oesophagus. However, a correlation between mast cell density (MCD) and either prognosis or angiogenesis has not been delineated yet in this disease. The aim of this study was to investigate the prognostic value of MVD and MCD in SCC of the oesophagus. The correlation between MVD and MCD was also evaluated. METHODS: MVD and MCD were investigated in tumour specimens from 53 patients diagnosed with SCC of the oesophagus. Intratumoral microvessels were stained with anti-CD34 antibody and mast cells with toluidine blue before being measured by light microscopy. RESULTS: Both MVD and MCD were associated with the depth of wall invasion, lymph node metastasis, and tumour progression (stage). A significant correlation was noted between MVD and MCD values (r = 0.72). The prognosis was significantly worse in patients with high MVD (> or = 92) and high MCD (> or = 18) values. Multivariate analysis indicated that MVD and stage were independent predictors of survival. CONCLUSIONS: These findings support the suggestion that MVD is a reliable prognostic marker in SCC of the oesophagus. Moreover, MCD may have a role in the angiogenesis of these tumours and might be responsible for their aggressive behaviour.

Clinicopathologic evaluation of CDw75 antigen expression in patients with gastric carcinoma.

Situated on mature B lymphocytes, CDw75 antigen is a sialylated carbohydrate epitope generated by the enzyme beta-galactosyl alpha-2,6-sialyltransferase. Although CDw75 antigen expression was found to be correlated with aggressive behaviour of tumour cells in gastric adenocarcinomas, its prognostic role still remains unknown. The objective of this study was to determine the value of CDw75 antigen expression as a marker of the metastatic potential and prognosis of gastric adenocarcinomas. CDw75 antigen expression was evaluated immunohistochemically in 64 tumours and their nodal metastases. The correlation was analysed between CDw75 antigen expression and selected clinicopathological variables, including survival. Positive staining was detected in 31 cases. Non-neoplastic gastric mucosa was consistently negative. CDw75 expression was correlated with larger tumour size (p<0.006), infiltrative growth pattern (p<0.044), advanced stage (p<0.0006), and positive lymph nodes (p<0.0003). The overall survival rate of patients with CDw75 expression was 28%, which was significantly worse than that of patients without CDw75 expression (53%) (p<0.0005). Multivariate analysis showed that CDw75 expression was an independent prognostic indicator, together with the growth pattern of the tumour. These results indicate that immunohistochemical detection of CDw75 antigen expression may be a good indicator of metastatic potential and of prognosis in patients with gastric carcinomas.

Microvessel count, proliferating cell nuclear antigen and Ki-67 indices in gastric adenocarcinoma.

The aim of the present study was to immunohistochemically investigate the prognostic value of neovascularization (expressed as microvessel count-MVC) and tumor cell proliferation (expressed as PCNA labeling index PLI and Ki-67 labeling index KLI) in gastric adenocarcinoma. Correlations with clinicopathologic features were also evaluated. Tumor specimens from 74 patients diagnosed as gastric adenocarcinoma were included in this study. Formalin fixed, paraffin embedded tissue sections stained immunohistochemically with F-VIII, PC10 and MIB-1 monoclonal antibodies. By ocular grid subdivided into 100 areas, number of microvessels and PC10, MIB-1 positive and negative cells were counted at x400 magnification. Chi-square test, Kaplan-Meier method and cox regression analysis were used for statistical analysis. The results showed that, MVC and PLI had a significant correlation with invasion and lymph node metastasis. The prognosis was significantly worse in patients with high MVC (>14 ) and with high PLI (>49%). However any relationship was not observed between KLI (38%) and clinicopathologic parameters, so KLI failed to predict the prognosis. Cox model showed that, MVC and PLI were independent prognostic variables. Ki-67 labeling index in gastric carcinomas has no prognostic relevance. However, the evaluation of microvessel count and proliferating cell nuclear antigen index in gastric carcinomas could be reliable indicators of prognosis.

Stereologic estimation of mean nuclear volume in well-differentiated adenocarcinoma and carcinoma in situ of the gallbladder.

OBJECTIVE: To investigate mean nuclear volume of cells in well-differentiated adenocarcinomas (20 cases) and carcinoma in situ (20 cases) of the gallbladder by the principle of estimation of the volume of particles with arbitrary shapes. STUDY DESIGN: Hematoxylin and eosin-stained, 4-micron-thick, vertical sections from formalin-fixed, paraffin-embedded tissue blocks were analyzed by using a projection microscope with a 100:1 oil immersion objective (NA 1.3); the final magnification was 2,500:1. The measurements were carried out in 10 microscopic fields for each slide. Mean nuclear volume was obtained by the stereologic method of point-sampled intercepts for vertical sections. RESULTS: Mean nuclear volume in well-differentiated adenocarcinomas (127.67 +/- 46.95 micron 3) was significantly larger than in carcinoma in situ (69.17 +/- 15.74 micron 3) (P < .000001). CONCLUSION: Stereologic estimation of mean nuclear volume may be helpful in the discrimination of malignant and borderline lesions of the gallbladder.