RESUMEN
Diploid tumour cells regularly continue to progress after the development of aneuploid cell populations in head and neck squamous cell carcinomas. The coexistence of aneuploid clones with their diploid progenitor cells provides a unique opportunity to study the order of appearance of p53 mutation and aneuploidy in the same tumour. Multiparameter flow cytometry was therefore applied to 22 oral squamous cell carcinomas to simultaneously assess cellular DNA content and p53 protein expression on a single-cell basis. Concurrent measurements of cytokeratin expression served to identify tumour cells of epithelial origin. One of 5 diploid and 2 of 17 aneuploid carcinomas were p53-negative. For 15 p53-positive aneuploid tumours, overexpression of p53 protein was identified for the aneuploid clones as well as for coexisting diploid tumour cell populations in 14 cases. On the understanding that coexisting diploid and aneuploid tumour cell populations have a common clonal origin, these results provide evidence that aneuploid tumour clones typically develop from p53-deficient diploid progenitor cells. Loss of wild-type p53 function may therefore contribute to the development of aneuploidy in head and neck cancer.
Asunto(s)
Aneuploidia , Carcinoma de Células Escamosas/química , ADN de Neoplasias/análisis , Citometría de Flujo , Genes p53 , Neoplasias de la Boca/química , Proteínas de Neoplasias/análisis , Células Madre Neoplásicas/patología , Proteína p53 Supresora de Tumor/análisis , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Transformación Celular Neoplásica/genética , Células Clonales/patología , Estudios de Cohortes , ADN de Neoplasias/genética , Diploidia , Progresión de la Enfermedad , Humanos , Queratinas/análisis , Neoplasias de la Boca/genética , Neoplasias de la Boca/patología , Proteínas de Neoplasias/biosíntesis , Neoplasias Faríngeas/química , Neoplasias Faríngeas/patología , Proteína p53 Supresora de Tumor/biosíntesisRESUMEN
The development of aneuploid clones from diploid progenitor cells is a regular characteristic of head and neck squamous cell carcinoma progression. While the significance of aneuploidy formation for the acquisition of invasive and metastatic behavior is well documented, little is known about the contribution of diploid tumor cells after aneuploid clones have emerged. To distinguish diploid cells of epithelial origin from benign cellular components, we applied multiparameter flow cytometry of DNA content and cytokeratin (CK) expression to 36 primary tumors. Twenty-seven carcinomas accommodated aneuploid cell lines that stained positive for CK. All diploid cell populations obtained from aneuploid carcinomas contained CK-positive subpopulations as did all of nine tumors that consisted exclusively of diploid cells. The proportions of CK-positive diploid cells ranged between 6% and 80%, independent of whether they were achieved from entirely diploid or from aneuploid carcinomas. CK-gated diploid and aneuploid cell populations showed largely identical S-phase fractions. These results emphasize that diploid tumor cells regularly persist after the development of aneuploid clones and significantly contribute to local tumor progression. Despite the presence of diploid epithelial cells in aneuploid primary tumors, exclusively the aneuploid clones of eight corresponding lymph node metastases were CK-positive. This provides further evidence of a largely reduced metastatic potential of diploid tumor cells.
Asunto(s)
Aneuploidia , Carcinoma de Células Escamosas/genética , Diploidia , Neoplasias de Cabeza y Cuello/genética , Carcinoma de Células Escamosas/química , Carcinoma de Células Escamosas/patología , Células Clonales/patología , Progresión de la Enfermedad , Células Epiteliales/patología , Citometría de Flujo , Neoplasias de Cabeza y Cuello/química , Neoplasias de Cabeza y Cuello/patología , Humanos , Técnicas In Vitro , Queratinas/análisisRESUMEN
Twenty-eight examples of papillary cystadenoma lymphomatosum (Warthin's tumour) of the parotid gland were analysed by high-resolution DNA flow cytometry. The mean coefficient of variation was found to be 1.19% (SD: 0.41). All tumours were DNA diploid. These results did not correspond with expected deviations based on published chromosomal studies. Also, the homogeneously low S-phase fractions (mean: 4.8%; SD: 2.7) found did not support the hypothesis of etiologically distinctive subgroups in these tumours.
Asunto(s)
Adenolinfoma/genética , ADN/análisis , Citometría de Flujo , Neoplasias de la Parótida/genética , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sensibilidad y EspecificidadRESUMEN
DNA flow cytometry studies of squamous cell carcinoma of the head and neck have shown that patients with diploid tumours have favourable prognoses, whereas the outcomes of those with DNA aneuploid tumours are poor. DNA flow cytometry is therefore increasingly used as an integral part of diagnostic procedures. To evaluate how representative biopsies predict the DNA ploidy of oral carcinomas, incisional biopsies taken pretherapeutically from 256 tumours were compared with the corresponding surgical resection specimens. Sixty-six tumours exclusively displayed cells with flow cytometrically diploid DNA content in both the biopsy and the subsequent resection specimen, while 182 carcinomas expressed DNA aneuploid tumour cell lines in matched samples. There were only 8 tumours (3.1%) with heterogeneity in the DNA ploidy status between the biopsy and the resection specimen. These results emphasise the usefulness of incisional biopsies to reliably prognosticate the DNA ploidy status of oral carcinomas.
Asunto(s)
Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , ADN de Neoplasias/genética , ADN de Neoplasias/metabolismo , Citometría de Flujo , Neoplasias de la Boca/metabolismo , Neoplasias de la Boca/patología , Biopsia , Estudios de Cohortes , Humanos , Ploidias , PronósticoRESUMEN
In a double blind trial the authors tested the assumption that magnesium potentiates by its specific action the therapeutic effect of anxiolytics. A group of 20 women treated on account of anxious depressive neurosis was divided into two sub-groups. The first was given anxiolytic and placebo, the second one anxiolytics and Mg-lactate in corresponding amounts. After 10 days the placebo and Mg-lactate were exchanged. Both groups were examined before treatment and then after 10 and 20 days of therapy by a series of psychological tests. It was revealed that the combination of anxiolytics and Mg-lactate leads to a more rapid reduction of psychopathological symptoms, in particular anxiety. In MAS and MHG tests the decline of anxiety was statistically significant at the level of p less than 0.05.