No abstract

Background: This trial evaluated whether preoperative short-course radiotherapy and consolidation chemotherapy (CCT) were superior to chemoradiation in rectal cancers with clinical (c)T4 or fixed cT3. Previously, we reported early results showing no differences in the radical surgery rate (primary end point). In the short-course/CCT group, we observed lower acute toxicity of preoperative treatment and better overall survival (OS). We updated results to determine whether the benefit in OS was sustained and to evaluate late complications.Patients and methods: Patients with cT4 or fixed cT3 rectal cancer were randomized either to preoperative 5 Â 5 Gy and three cycles of FOLFOX4 or to chemoradiation (50.4 Gy with bolus 5-Fu, leucovorin and oxaliplatin).Results: Patients (N ¼ 515) were eligible for analysis, 261 in the short-course/CCT group and 254 in the chemoradiation group. The median follow-up was 7.0 years. The difference in OS was insignificant [hazard ratio (HR) 0.90; 95% confidence interval (CI) 0.70-1.15; P ¼ 0.38). However, the difference in early OS favouring short-course/CCT previously reported was observed again, being 9% at 3 years (95% CI 0.5% to 17%). This difference disappeared later; at 8 years OS was 49% in both groups. There was no difference in disease-free survival (HR 0.95; 95% CI 0.75-1.19; P ¼ 0.65) at 8 years 43% versus 41% in the short-course/CCT group versus the chemoradiation group, respectively. The corresponding values for cumulative incidences of local failure and distant metastases did not differ and were HR ¼ 1.08, 95% CI 0.70-1.23, P ¼ 0.60, 35% versus 32% and HR ¼ 1.10, 95% CI 0.68-1.23, P ¼ 0.54, 36% versus 34%, respectively. The rate of late complications was similar (P ¼ 0.66), grade 3þ being 11% versus 9% in the short-course/CCT group versus the chemoradiation group, respectively. Conclusion:The superiority of preoperative short-course/CCT over chemoradiation was not demonstrated.

Determination of oestrogen receptor alpha (ER) represents at present the most important predictive factor in breast cancers. Data of ours and of other authors suggest that promising predictive/prognostic factors may also include pS2, metallothionein (MT) and CD24. Present study aimed at determining prognostic and predictive value of immunohistochemical determination of ER, pS2, MT, and CD24 expression in sections originating from 104 patients with breast cancer. An univariate and multivariate analysis was performed. Both univariate and multivariate analyses demonstrated that cytoplasmic-membranous expression of CD24 (CD24c-m) represents a strong unfavourable prognostic factor in the entire group and in most of the subgroups of patients. In several subgroups of the patients also a prognostic value was demonstrated of elevated expression of pS2 and of membranous expression of CD24. Our studies demonstrated that all patients with good prognostic factors (higher ER and pS2 expressions, lower MT expression, CD24c-m negativity) survived total period of observation (103 months). The study documented that cytoplasmic-membranous expression of CD24 represented an extremely strong unfavourable prognostic factor in breast cancer. Examination of the entire panel of the studied proteins permitted to select a group of patients of an exceptionally good prognosis.

Elevated metallothionein (MT) expression in ovarian cancers treated with cisplatin-based schemes represents an unfavorable prognostic index. MT expression is significantly higher in tumor samples obtained after chemotherapy. The present study aimed at examining MT expression in ovarian carcinoma cells sensitive (A2780) or resistant (A2780RCIS) against platinum drug treatment as well as examining effects of exposure to cisplatin on MT expression. Subcellular expression of MT was evaluated also in samples originating from 73 ovarian tumors. Cisplatin-resistant A2780RCIS cells were exposed to increasing cisplatin concentrations, and the subcellular expression of MT was determined by immunocytochemistry. The studies demonstrated that cisplatin-resistant A2780RCIS cells exposed to cisplatin typically manifested a nuclear MT expression. The study demonstrated also that exposure to cisplatin was paralleled by growing MT expression in cell nuclei. The nuclear expression of MT was also found to be specific for ovarian cancers of poor clinical outcome. No relationship could be demonstrated between cytoplasmic expression of MT and clinical variables. Nuclear MT expression is induced by cisplatin and seems to protect DNA in the cells from toxic effects of the drug.

The membrane cofactor protein, CD46 represents a complement inhibitor, which protects autologous cells from complement-mediated cytotoxicity. On tumor cells, CD46 may exhibit the potential to protect them from immune responses of the host. The present study aimed at evaluation of prognostic significance of CD46 expression in breast cancers. The analyses were performed on 70 samples of breast cancer. Immunohistochemical reactions were performed on paraffin sections of studied tumors using monoclonal antibodies directed against CD46. Results of the immunohistochemical reactions and of clinical observations were subjected to statistical analysis. Multivariate analysis showed that expression of CD46 and involvement of lymph nodes represent independent risk factors for disease-free survival and overall survival. Kaplan-Meier analysis showed that patients with tumors negative for CD46 have an increased progression-free time and overall survival time as compared with patients with the CD46-positive tumors. The study demonstrates that breast cancers manifest CD46 expression and that it is linked to a less favorable prognosis.