Immunohistochemical expression of bcl-2 in Dukes' stage B and C colorectal carcinoma patients: correlation with p53 and ki-67 in evaluating prognostic significance.

The objective of this study was to evaluate the expression of bcl-2 in Dukes' stage B and stage C (AJCC/UICC stage I and III) colorectal adenocarcinomas and to examine its association with clinicopathological features, p53, ki-67 and long term outcome. Paraffin embedded specimens from 61 patients with Dukes' stage B (AJCC/UICC stage I) and 39 patients with Dukes' stage C (AJCC/UICC stage III) colorectal adenocarcinoma who were treated with surgery were assessed. We used immunohistochemistry to determine the expression of bcl-2, p53 and ki-67 with a five-year follow-up. Positive bcl-2 expression was seen in 27 cases (27%). Expression of bcl-2 protein was related to tumor stage (p=0.0117). There was very strong evidence of an association between bcl-2 staining and ki-67 score (p<0.001). There was a trend towards increased survival in patients whose tumors expressed bcl-2 protein (p=0.001). When entered into a multivariate analysis model, which also included p53 and stage, bcl-2 staining emerged as a prognostic indicator variable. Expression of bcl-2 appears to be useful in selecting a group of colorectal cancer patients with a better prognosis.

Loss of cardioprotection induced by ischemic preconditioning after an initial ischemic period in isolated rat hearts.

BACKGROUND: The beneficial effect of ischemic preconditioning (PC) has been extensively studied in normal hearts but its effects on diseased hearts remain largely unknown. The effect of PC in the already ischemic myocardium has not been previously studied, although ischemia in varying intervals, which is difficult to assess, is often encountered in clinical practice. OBJECTIVE: To investigate whether the cardioprotective effect of PC is preserved when it is applied after a period of ischemia of varying duration. METHODS: Male Wistar rats were used for this study. Isolated normal rat hearts were perfused in Langendorff mode. Before 20 min of zero flow global ischemia followed by 45 min of reperfusion, hearts were subjected to an initial 20-min period of ischemia followed by 10 min of reperfusion (group A1); an initial 20-min period of ischemia followed by 10 min of reperfusion and two-cycle PC (3 min of ischemia, 5 min of reperfusion followed by 5 min of ischemia and 5 min of reperfusion) (group A2); and two-cycle PC followed by the initial 20-min period of ischemia and 10 min of reperfusion (group A3). Groups B and C were subjected to an initial ischemia of 15 min and 10 min, respectively, and subgroups 1, 2 and 3 were treated as above. Left ventricular end-diastolic pressure was measured at 45 min of reperfusion (LVEDP45 in mmHg). Postischemic recovery of left ventricular developed pressure was expressed as a percentage of the initial value (LVDP%). RESULTS: LVDP% and LVEDP45 were similar between groups A1 and A2, while when ischemic preconditioning preceded the two periods of ischemia (group A3), it resulted in significantly higher LVDP% and significantly lower LVEDP45 compared with groups A1 and A2. Left ventricular functional recovery was not increased in group B2 compared with group B1. LVDP% and LVEDP45 were similar among groups C1, C2 and C3. CONCLUSION: Ischemic preconditioning does not improve functional recovery in isolated rat hearts that have been initially subjected to 20 min or 15 min of zero-flow global ischemia, while an initial 10-min ischemic period seems to precondition the heart.