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Resumen La leucemia/linfoma de celulas T del adulto es una neoplasia de linfocitos T causada por el retrovirus humano HTLV-1, con manifestaciones sistemicas y cutaneas muy variables. El HTLV-1 afecta a mas de 5-10 millones de personas en el mundo y su distribucion geografica en zonas endemicas se encuentra intimamente ligada a la prevalencia de leucemia/linfoma de celulas T del adulto. Existen distintas variantes en funcion de su presentacion clinica siendo las de peor pronostico la aguda y el linfoma. El diagnostico diferencial presenta dificultades debido a la inespecificidad de los sintomas. En el laboratorio de analisis clinicos la sospecha diagnostica es mediante el estudio citologico en sangre periferica con la observacion de celulas caracteristicas del leucemia/linfoma de celulas T del adulto.

Background: Methylation of the CpG islands in the p16 gene promoter region is an important transcription repression mechanism that has been identified as an alternative mechanism for inactivating specific genes in cancer. Given that, DNA methylation is a common event in colorectal cancer. Materials and Methods: The aim of this study was to establish the methylation status of the p16 gene in 104 patients with colorectal carcinoma and evaluate its prognostic value. DNA was bisulfite-modified and analyzed for p16 promoter methylation by methylation-specific PCR. Results: Methylation of thep16 gene was determined in 18.3% of our patient population (19/104). The methylated state did not correlate with any clinicopathological factors. During a median follow-up period of 72 months, the overall survival rate for patients with gene methylation was 75% and without gene methylation it was 61% (p = 0.09). Conclusions: Although not statistically significant, this difference indicates a clinically valuable tendency.

Resumen La importancia sociosanitaria del cancer de pulmon radica en su elevada incidencia y mortalidad. En la actualidad se considera el cancer como el resultado de una acumulacion de alteraciones que afectan a diversos genes con distintas funciones celulares. Diversos estudios geneticos han demostrado una perdida de material genetico en la region 21 del brazo corto del cromosoma 9 (9p21), siendo una de las alteraciones geneticas mas frecuentemente identificadas en el cancer humano. Esta region contiene un gen supresor llamado p16, que codifica las proteinas p16 y p19. Se estudio una serie de 98 pacientes diagnosticados de carcinoma de pulmon no microcitico. Se analizo la perdida de heterozigosidad (LOH) en 9p21 mediante el analisis de polimorfismos de microsatelites. El 23,5% de los pacientes presentaba LOH y/o inestabilidad en 9p21. Contrariamente a lo que se esperaba, los pacientes que no presentaban alteraciones geneticas en p16 tenian un riesgo relativo de fallecer 1,7 veces mayor (p = 0,1) que los que si presentaban LOH y/o inestabilidad.

3% of human cancers are renal cell carcinomas (RCC). The most common chromosome abnormality found in this tumor is loss of heterozygosity (LOH) on the short arm of chromosome 3, which suggests that there must be one or more tumor suppressor genes between 3p14 and 3p21 near the VHL gene which play a relevant role in renal cancer development. DNA from normal and tumor tissue from 40 patients at various stages of RCC was analyzed for LOH at three microsatellites mapped to 3p (3p14.1–14.3; 3p21.2–21.3 and 3p25) by polymerase chain reaction). 42.5% of the tumors studied showed LOH on at least one locus. 30% showed LOH on only one locus; 5% on two loci and 7.5% on the three loci tested. LOH occurred only on nonpapillary tumors (p = 0.03). Interestingly, all the tumors with LOH on 3p21 were ≥25 mm (p = 0.04; relative risk 1.76, confidence interval: 1.3–2.3).

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. © 1999 Cancer Research Campaign

Background The CellSearch System is a technique to detect circulating tumor cells (CTCs) in patients with cancer. Few data have been published concerning the role of CTCs detection by this method in colorectal cancer. The aim of this study was to correlate the presence of CTCs with the commonest clinical and morphological variables. Patients and methods Blood samples were collected from 97 patients and 30 healthy volunteers. Quantification of CTCs in 7.5 ml of blood was carried out with the CellSearch System. The results were expressed as number of CTCs/7.5 ml and the cut-off of ≥2 CTCs/7.5 ml was chosen to define the test as positive. Results Positive CTCs were detected in 34 of 94 patients (36.2%). Correlation was not found among positive CTCs and location of primary tumor, increased carcinoembryonic antigen level, increased lactate dehydrogenase level or grade of differentiation. Only stage correlated with positive CTCs (20.7% in stage II, 24.1% in stage III and 60.7% in stage IV, P = 0.005). Conclusions CTCs detection by CellSearch is a highly reproducible method that correlates with stage but not with other clinical and morphological variables in patients with colorectal cancer. Colon cancer tumor cells are detectable in all stages. Further studies are warranted.

The relationship between breast cancer and circadian rhythm variation has been extensively studied. Increased breast tumorigenesis has been reported in melatonin-suppressed experimental models and in observational studies.Circulating Tumor Cells (CTC) circadian- rhythm may optimize the timing of therapies. This is a prospective experimental study to ascertain the day-time and night-time CTC levels in hospitalized metastasic breast cancer (MBC) patients.CTC are isolated and enumerated from a 08:00 AM and 08:00 PM blood collections. 23 MBC and 23 healthy volunteers entered the study. 69 samples were collected (23 samples at 08:00 AM and 23 samples at 08:00 PM from MBC; 23 samples from healthy volunteers). Results from two patients were rejected due to sample processing errors. No CTC were isolated from healthy-volunteers.No-differences between daytime and night-time CTC were observed. Therefore, we could not ascertain CTC circadian-rhythm in hospitalized metastasic breast cancer patients.

The amplification and/or overexpression of the c-erbB-2/neu oncogene may play a role in tumor development and progression. The aim of this prospective study was to evaluate the prognostic value of p185 protein in colorectal cancer using immunohistochemical techniques. We analyzed 106 colorectal tumor tissue specimens from patients who had been operated on by the same surgeon and subjected to a median follow-up of 3 years. Thirty-three per cent of patients showed p185 overexpression related to an advanced stage of the disease. In patients with adenocarcinoma tumors of the colon without distant metastases, p185 detection was found to be of clinical prognostic relevance (p = 0.06).

To investigate the possible role of genomic aberrations of chromosome 9p21 in the tumorigenesis of human renal cell carcinoma (RCC), 40 sporadic RCCs were studied using PCR analyses. The tumours were predominantly low stage and low grade. Loss of heterozygosity (LOH) was observed in nine of 39 informative cases, but no homozygous deletion was noticed. Hypermethylation of the promoter region of p16 occurred in eight of the 40 RCCs. No correlation was found between hypermethylation of the p16 gene and LOH on 9p21. A similar level of LOH and methylation was observed in the 40 RCCS regardless of histology, grade and stage. These results suggest that inactivation of p16 and the possibility of other unknown tumour suppresser genes located on other chromosomes could be involved in the pathogenesis of RCC.

To determine the utility of p185 oncogene in the biological characterization of transitional cell carcinoma and in the prediction of recurrence, and to analyze survival at 5 years mean follow-up.A prospective clinical cohort study was conducted on 81 patients. Tissue specimens were obtained between November 1992 and November 1993. The study comprised two groups: nontumoral bladder tissue specimens from 20 patients (group I) and tissue specimens from 61 patients with bladder carcinoma (group II). p185 expression was determined by enzyme immunoanalysis (EIA). A statistical analysis of the results was performed.p185 oncoprotein levels were higher in patients with recurrence (1098.97 HNU/mg protein vs. 924.54 HNU/mg). Although higher levels of p185 were found in the patients that had died vs those who are alive, the differences were not statistically significant for overall survival or stratification by tumor grade or infiltration (p = 0.556; ns).Determination of p185 oncoprotein was found to be useful in the prediction of tumor recurrence at 5 years mean follow-up.

Renal cancer accounts for 2% of tumors. The most common chromosome abnormality found in renal cancer is the loss of heterozygosity (LOH) on the short arm of chromosome 3 (3p), which suggests that near the gene responsible for von Hippel-Lindau disease, there may be one or more tumor suppressor genes between 3p14 and 3p21 with a relevant role in the development of renal cancer.41 patients with sporadic renal cancer were tested for three microsatellites mapped to the short arm of chromosome 3 (3p14.1-3p14.3, 3p21.2-3p21.3 and 3p25) by polymerase chain reaction. The results were compared with patient habits and tumor features.43.9% of the patients showed LOH on at least one locus. Thirty-four percent showed LOH only on one locus, 4.9% on two loci and 7.3% on the three loci tested. All the patients who showed LOH on 3p21 had a tumor size greater than 25 mm. There is a risk 1.76 times higher of no loss in tumors less than 25 mm in size than in tumors greater than 25 mm (Cl 95% 1.33-2.33).

BACKGROUND AND OBJECTIVE: The aim of this study is the detection and quantification of circulating tumor cells (CTC) in patients diagnosed with colon cancer and to establish whether they are related to the main clinicopathologic variables for this type of carcinoma. PATIENTS AND METHOD: Twenty-five colon cancer patients and 30 healthy volunteers were analysed. The quantification was performed using the CellSpotter Analyzer (Veridex LLC), that allows immunomagnetic isolation and immunospecific labelling of the cells for their enumeration. RESULTS: 72% of the colon cancer patients showed CTC and the mean number of cells found was 5 CTC/7.5 ml of peripheral blood. 52% of the samples contained 2 or more cells. Considering 2 cells as the cut-off point, a significant relationship with lactate dehydrogenase was found. CONCLUSIONS: This new technology which allows isolation and quantification of CTC in peripheral blood has proven to be valid for the detection of epithelial cells in colon cancer patients in every tumor stage. The results shown in this work confirm that cytokeratin 8, 18 and 19 are detected in CTC in this tumor type and will allow us to develop a protocol for the study of the relationship of quantification of theses cells and the clinical parameters involved in colon cancer.

AIM: To determine whether the telomerase activity is related to the Microsatellite instability (MSI) genetic pathway and whether it means a difference in the survival. METHODS: The population consisted of 97 colorectal cancer patients. MSI determination was performed in accordance with the NCI criteria using PCR and Genescan. Telomerase activity was determined by the TRAP-assay, an ELISA procedure based on the amplification of telomeric repeat sequences. RESULTS: 6.2% showed high MSI (MSI-H), 10.3% showed low MSI (MSI-L) and 83.5% did not show this alteration (MSS). Positive telomerase activity was detected in 92.8% of the patients. 83.3% of MSI-H tumors showed positive telomerase against 93.8% of MSS tumors. In the overall survival analysis the absence of telomerase activity conferred a better prognosis. CONCLUSION: Previous works have shown that tumors which develop via the MSI pathway present a better prognosis. No link between telomerase activity and MSI status is observed, although sample sizes are small. Patients with telomerase negative tumors had better overall survival than patients with telomerase positive tumors.