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Objective: To determine the loss of heterozygosity (LOH) on 9p21 (locus D9S1747) in patients with renal carcinoma by analysis of microsatellite polymorphisms., Methods: 40 patients with sporadic renal cancer were studied. LOH on 9p21 was performed by analysis of microsatellite polymorphisms., Results: 23.7% showed LOH on 9p21. No correlation was found between this genetic alteration and tumor features., Conclusions: LOH on 9p21 was found in 23.7% of the patients in this series. LOH was found in 26.9% of renal cell carcinomas, 25% of papillary carcinomas and 25% of Bellini duct carcinomas. LOH was not found in the other histological types.

Objective: To determine the methylation status of the tumor suppressor gene p16 in patients with renal carcinoma by analysis of microsatellite polymorphisms., Methods: 40 patients with sporadic renal cancer were studied. Tumor and normal tissue from each patient were tested for methylation status of the p16 gene by analysis of microsatellite polymorphisms., Results: 20% showed methylation of p16. No correlation was found between this genetic alteration and tumor features., Conclusions: Methylation of p16 was found in 20% of the patients in this series. According to the analysis, 18.5% of renal cell carcinomas showed methylation, 50% of chromophobe cell carcinomas and 25% of carcinomas of Bellini's tubules. The rest of the histological types showed no methylation.

The possible interaction between the quantified overexpression of the oncoproteins p53 and p185 was evaluated. These proteins have already been independently defined as prognostic factors in non-small-cell lung cancer (NSCLC). p53 and p185 levels were determined in stage I patients (n = 40) from a sample of 102 NSCLC sufferers who underwent surgery for precocious disease during the period October 1991 to June 1994. The resected tumors were histologically classified and included 15 adenocarcinomas (37.5%), 1 large-cell carcinoma (2.5%), and 24 epidermoid (60%) carcinomas. The p53 concentration of tumor specimens was determined by luminescence immunoanalysis and was defined as positive if it was above the minimum value detectable by the method (0.01 ng/mg). The p185 protein was quantified by enzyme-linked immunoassay, and the 80th percentile of the frequency distribution was used as the reference cutoff value (348.8 U/mg). Survival and disease-free-survival (DFS) rates were estimated at 24 months after intervention. There were no significant differences in survival or DFS of patients with adenocarcinoma-type tumors for subjects with independent p185 values < 348.8 U/mg and those showing values >/= 348.8 U/mg. Neither were there differences observed between patients with positive and negative p53 values. In patients with epidermoid-type tumors the cumulative survival was significantly higher in p53-negative than in p53-positive patients (p = 0.03) and was also higher in patients with p185 levels < 348.8 U/mg than in those with values >/= 348.8 U/mg (p = 0.00001). These patients showed no significant differences with respect to recurrence rate. The possible synergistic behavior of p53 and p185 levels as a prognostic factor was evaluated in patients with epidermoid-type tumors. p53-negative and p53-positive patients were grouped according to a p185 level of less than or more than 348.8 U/mg. Significant differences were seen in both survival rates and DFS between groups. Individual analysis of relative risks showed an increased risk of death and greater recurrence rate in patients with p185 levels >/= 348.8 U/mg and a greater recurrence rate in patients with p53-positive values. Multivariate analysis established that the multiplicative, synergistic, prognostic effect of p53 and p185 was not significant. The existence of a significant, synergistic, prognostic effect of the p185 and p53 proteins in NSCLC could not be proven. However, a greater prognostic potential of the quantified overexpression of p185 with respect to that of p53 was established. An additive effect in the prognostic potential of both proteins was also observed (stratified analysis).

The expression of p53 protein was examined in a series of 111 colorectal cancer adenocarcinomas with a long follow-up. A quantitative luminometric immunoassay (LIA) was used for the measurement of wild-type and mutant p53 protein in extracts from colorectal tumour cytosols, p53 being detected in 42% of the samples (range 0.0-52 ng (mg-1)). Using an arbitrary cut-off value of 2.7 ng mg(-1), 25% of the tumours were classified as manifesting high p53 levels. There was no association of p53 expression with patient age, sex, serum preoperative carcinoembryonic antigen (CEA) levels, tumour site and size, nodal status or TNM stage. Significant and independent correlation was found to exist between high p53 levels and prolonged disease-free survival (P = 0.05) at a median follow-up of 60 months. This survival advantage was most apparent among stage III cancer patients. The results from this study would suggest that expression of high p53 levels appear to be useful in selecting a group of colorectal cancer patients with a better prognosis.

Background: Recent advances on carcinogenesis have led to the recognition of different patterns of behaviour of non-small cell lung cancers apart from those guided by the TNM staging system and the histologic subtype. The frequent genetic loss on chromosome 3p in all kinds of lung carcinoma leads to the suspect of the presence of a tumor suppressor gene located in that place. The aim of this work was to compare the different clinical features and evolution after treatment of the patients with non small cell lung carcinoma with and without loss of heterozygosity (LOH) on 3p., Patients and Method: Forty-five operated on non-small cell lung cancer patients were evaluated. The mean age was 64.4 years and all the patients were male. Seven patients had been previously treated for another epithelial neoplasm. 82.2% of the patients were heavy tobacco smokers. Most of the tumors (62.2%) were squamous cell carcinomas. Samples of tumoral and non tumoral lung tissue were immediately frozen after surgery. DNA from the tissue was extracted; then PCR amplification of microsatellites in regions 3p14 and 3p21 was performed. To determine the LOH in the regions analyzed a polyacrylamide gel electrophoresis was performed., Results: Twenty-five percent of the informative samples for 3p14 and 21.9% for 3p21 showed LOH. There was an statistical relationship between the LOH on 3p14 and the history of tobacco smoking and the adenocarcinoma histologic subtype (p < 0.05). There was a higher number of relapses and a shorter disease-free interval in those patients harboring 3p21 LOH., Conclusions: LOH on 3p can be detected in non-small cell lung carcinoma. Patients with loss of heterozygosity on 3p21 have a worse evolution after a curative intended surgical resection.