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Eleven wood-workers with sinonasal adenocarcinoma were analyzed by comparative genomic hybridization. This technique serves as a screening test for regions of copy number changes in tumor genomes. We have applied the technique to map DNA gains and losses in 9 cases of formalin-fixed, paraffin-embedded tumors and 2 cases of frozen tumors. Gains were found most frequently than losses. Whole arm chromosomic gains were detected in high frequencies at 8q, 7q, 12q and 18p and losses at 18q, 8p, 10q, 5q, 14q and 17p. The segment most frequently amplified was 18p11.1-q11 (45%), even though others like 7q21-22 (18%) were related with lower survival rates. This analysis allows us to know for the first time the chromosomic aberrations that occur and may play an important role in sinonasal adenocarcinoma. In the future, comparative genomic hybridization could be used in the woodworkers with long exposition to wood dust to detect initial genetic aberrations and obtain an early treatment and diagnosis of the disease.

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Se estudian 11 pacientes trabajadores de la madera que desarrollaron adenocarcinomas nasosinusales. Se utilizó la hibridación genómica comparativa como método de análisis en el conjunto del contenido genómico en 9 tumores parafinados y 2 tumores congelados.Encontramos alteraciones en todos los casos predominando las ganancias cromosómicas frente a las pérdidas. Las ganancias más frecuentes de brazos cromosómicos se observan en 8q, 7q, 12q y 18p y las pérdidas o deleciones en 18q, 8p, 10q, 5q, 14q y 17p. El mayor número de amplificaciones se encontró en 18p11.1-q11 (45 por ciento), aunque otras como 7q21-22 (18 por ciento) se relacionaron con menor supervivencia. Por primera vez, este análisis permite conocer las alteraciones cromosómicas ocurridas en los adenocarcinomas nasosinusales y es un primer paso en el diseño de un modelo de progresión. En un futuro, la hibridación genómica comparativa podría ser utilizada en trabajadores expuestos al polvo de madera para detectar las alteraciones genéticas iniciales y contribuir al diagnóstico y tratamiento precoz de la enfermedad. (AU)

Eleven wood-workers with sinonasal adenocarcinoma were analyzed by comparative genomic hybridization. This technique serves as a screening test for regions of copy number changes in tumor genomes. We have applied the technique to map DNA gains and losses in 9 cases of formalin-fixed, paraffin-embedded tumors and 2 cases of frozen tumors. Gains were found most frequently than losses. Whole arm chromosomic gains were detected in high frequencies at 8q, 7q, 12q and 18p and losses at 18q, 8p, 10q, 5q, 14q and 17p. The segment most frequently amplified was 18p11.1-q11 (45%), even though others like 7q21-22 (18%) were related with lower survival rates. This analysis allows us to know for the first time the chromosomic aberrations that occur and may play an important role in sinonasal adenocarcinoma. In the future, comparative genomic hybridization could be used in the woodworkers with long exposition to wood dust to detect initial genetic aberrations and obtain an early treatment and diagnosis of the disease (AU)

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Lymph node metastases in pharyngolaryngeal squamous-cell carcinoma are the clinical finding that most precisely condition prognosis. Sometimes the presence of subclinical metastases modifies the initial therapeutic strategy because they are not detected by physical exploration or imaging techniques. We tried to establish a relationship between the tumor's intrinsic aggressiveness and the development of metastases through tumoral DNA damage. Aneuploidy and the S phase were more frequent in tumors of the larynx, particularly supraglottic tumors, that developed lymph node metastases (72%) than in diploid tumors with a normal S phase (18%). In pharyngeal tumors, no differences could be established because most were aneuploid with a high S phase and metastases. Flow cytometry is highly sensitive, but not sufficiently specific for routine clinical use. However, it is a useful point of departure for our line of research, which will continue with a search for more specific genetic or molecular markers of metastases among the general DNA abnormalities.

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Las metástasis ganglionares en los carcinomas epidermoides faringolaríngeos son el dato clínico que condiciona el pronóstico de forma más precisa. En ocasiones la presencia de metástasis subclínicas hace que el planteamiento inicial se vea alterado al no poder ser detectadas en la exploración ni por las técnicas de imagen. Se trató de establecer una relación entre la agresividad intrínseca del tumor y el desarrollo de las metástasis teniendo en cuenta el daño del ADN tumoral. Utilizando la aneuploidía y el aumento de la fase S podemos observar cómo los tumores laringeos, sobre todo los supraglóticos, presentan esta alteración de forma más significativa, cuando desarrollan metástasis ganglionares (72 por ciento) en relación a los tumores diploides y con fase S normal (18 por ciento). En los tumores laríngeos no es posible establecer diferencias pues la mayoría son aneuploides con fase S alta y metastásicos. El procedimiento de la citometría de flujo tiene alta sensibilidad pero es poco específico para aplicar en la clínica de forma rutinaria. Aunque nos sirve de partida para abrir esta línea de investigación, debemos buscar otros marcadores genéticos o moleculares más específicos del proceso de metástasis dentro de la alteración general del ADN (AU)

Lymph node metastases in pharyngolaryngeal squamous-cell carcinoma are the clinical finding that most precisely condition prognosis. Sometimes the presence of subclinical metastases modifies the initial therapeutic strategy because they are not detected by physical exploration or imaging techniques. We tried to establish a relationship between the tumor's intrinsic aggressiveness and the development of metastases through tumoral DNA damage. Aneuploidy and the S phase were more frequent in tumors of the larynx, particularly supraglottic tumors, that developed lymph node metastases (72%) than in diploid tumors with a normal S phase (18%). In pharyngeal tumors, no differences could be established because most were aneuploid with a high S phase and metastases. Flow cytometry is highly sensitive, but not sufficiently specific for routine clinical use. However, it is a useful point of departure for our line of research, which will continue with a search for more specific genetic or molecular markers of metastases among the general DNA abnormalities (AU)

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OBJECTIVE: To analyze the prognostic significance in bladder carcinoma of DNA ploidy and cell phase fractions measured by bladder wash flow cytometry. METHODS: Samples were obtained from 25 patients by bladder irrigation; 16 before surgery and 9 during follow-up cystoscopic examination. Cells were stained with propidium iodide and analyzed with the FacScan flow cytometer and Cellfit 2.01 (Becton-Dickinson). RESULTS: The number of cells obtained was sufficient for flow cytometric analysis in all cases. In 13 tumor samples (8 superficial and 5 invasive tumors), aneuploidy cells were detected in 3 cases that had a worse outcome; the only superficial tumor in which aneuploidy was detected presented a recurrent bladder carcinoma 15 months later. Of the 5 patients with invasive tumors, two patients with aneuploidy died within 6 months from tumor metastases. Of the patients without macroscopic tumor, only one showed an increase in the percentage of the S phase fraction (19.5% of cells in S phase). A recurrent bladder carcinoma was detected in this patient 6 months after the analysis. In patients with macroscopic tumor, analysis of the S phase fraction was not relevant for prognosis. CONCLUSIONS: Analysis of DNA ploidy and cell phase fractions by flow cytometry of bladder washings can increase the prognostic information in bladder carcinoma. Aneuploidy was associated with a worse prognosis and an increase in the S phase fraction predicted a recurrent bladder carcinoma months before it manifested clinically.

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OBJECTIVE: To establish prognostic models and protocols for individualized management in colorectal carcinoma patients based on both clinical and DNA flow cytometric parameters. STUDY DESIGN: Prospective study of 88 colon carcinoma patients with a minimum follow-up of 12 months, operated on with the intent to cure and not treated with radiotherapy or chemotherapy. All the cases were subjected to a clinical evaluation: age, sex, tumor localization and size, histologic grade, tumor stage, disease-free interval, survival and flow cytometric study (ploidy, DNA index and S-phase fraction [SPF]). RESULTS: From the total of 88 neoplasms studied, 56 (63.6%) were from males and 32 (36.4%) from females; 30 (34%) were located in the right side of the colon, 7 (8%) in the transverse colon and 51 (58%) in the left side of the colon. Eleven (12.5%) were stage I, 52 (59.1%) stage II and 25 (28%) stage III. Forty-two (47.7%) were diploid and 46 (52.3%) aneuploid. The S-phase mean was 14.6% (12% for diploids and 16.9% for aneuploids). During the follow-up period, 26.1% of diploid tumors recurred, whereas aneuploid tumors recurred in 36.9% (P < .05). SPF from diploid and aneuploid tumors was analyzed separately. CONCLUSION: Regarding relapse-free interval, the behavior of diploid tumors with a high SPF was similar to that of aneuploid ones. Two kinetic profiles were established, favorable (diploid tumors with low S phase) and unfavorable (diploid with high S phase and all aneuploid tumors), that had significant prognostic value for progression and survival and that allowed identification of patients at high risk of recurrence. We formulated a prognostic index according to SPF and tumor stage that has discriminatory capacity for biologic behavior in colorectal tumors.

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Flow Cytometry (FC) has been incorporated into cancer research in relation to its prognostic value together with histological parameters and TNM stages. We have studied by means of FC the cell cycle of 132 samples from male patients with Squamous Cell Lung Carcinoma (SQCLC). All of the patients received curative surgery and the clinical follow-up was 60 months. The clinical and cytometric parameters were evaluated in order to predict the patients' outcome. The presence of tumoural recurrence and the tumoural stage showed statistical significance associated with survival. The multivariant analysis reveals radiotherapy (p = 0.004) as protective variable and the high S-phase fraction (SPF) (p = 0.001) and stage IIIA (p = 0.012) as risk factors. The SPF appears as an independent prognostic factor for overall survival time. We can build a prognostic index representative of different prognostic groups, which allows us to improve the individual monitoring of these patients.

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