Glucose metabolism enzymes gene expression analysis and selective metabolic advantage in the clinical progression of colorectal cancer (CRC)

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Comparison of computerized analysis of nuclear DNA changes in uterine cervix dysplasia and in urothelial non-invasive papillary carcinoma.

The nuclear DNA content was measured in preneoplastic lesions of the uterine cervix and in papillary carcinomas of the bladder. Three groups of features were calculated from the raw data: basic DNA, DNA deviation and DNA distribution. The basic DNA features, concerning both the cervix and the bladder, showed a progressive increase in the mean DNA content, a decrease in the percentage of diploid nuclei and steadily increasing values of polyploid and aneuploid nuclei. Among the DNA deviation features, the malignancy grade value was zero in the normal cervical epithelium and in the normal urothelium. An increase in this value was evident in moderate dysplasia and in urothelial papillary carcinoma of grade 2, the highest value being in CIS and in grade 3. Concerning the DNA distribution features, the values of the 15th and 95th percentiles and their difference were progressively higher both in the cervix and in the bladder, expressing a continuous shift and spread of the DNA content measurements in the different diagnostic categories, with respect to normal epithelium and urothelium. The statistical analysis showed that the strongest correlation is between 2c D.I. and % of polyploid nuclei in the cervix and between M.I. and % of aneuploid nuclei greater than 4c in the bladder. In the cervix the most discriminating feature is the Malignancy Grade, whereas in the bladder it is the percentage of diploid nuclei. The comparison between the results of the three groups of features showed that: 1) Mild dysplasia of the cervix and urothelial papillary carcinoma of grade 1 showed similar changes in DNA features. Both were basically characterized by increased proliferative activity

Loss of hMLH1 expression correlates with improved survival in stage III-IV ovarian cancer patients

Pre-clinical data suggest a relationship between DNA MisMatch Repair (MMR) system failure, particularly the inactivation of genes hMLH1 and hMSH2, and resistance to drugs like cisplatin and carboplatin. We studied the correlation between loss of hMLH1 expression in tumour cells and clinical outcome in 38 patients with ovarian cancer, who underwent cisplatin-based chemotherapy. 19 patients (56%) showed loss of hMLH1 expression (Group A) while 15 patients (44%) showed normal hMLH1 expression (Group B). 4 patients were not evaluable for hMLH1 expression. The 2 groups of patients were similar for clinical characteristics, response to chemotherapy and time to progression. Group A patients showed a median survival of 55 months whereas Group B patients had a median survival of 12 months (P=0.014). Loss of hMLH1 expression was the only independent predictor of survival in the multivariate analysis. Our observations suggest a relationship between loss of hMLH1 and improved survival in advanced ovarian cancer. (C) 2003 Elsevier Science Ltd. All rights reserved