RESUMEN
BACKGROUND: Cervical cancer (CeCa) is the second most common cancer in women in developing countries, and human papilloma virus (HPV) is the primary etiological factor. Aberrant expression of HOX transcription factors has been observed in several types of cancer. To date, however, no reports exist on the expression of HOXB2 and HOXB13 proteins during neoplastic progression in CeCa and its correlation with HPV infection. MATERIALS AND METHODS: Expression of HOXB2 and HOXB13 proteins was assessed in tissue microarrays from normal cervical epithelium, cervical intraepithelial neoplasias grade 1-3, and CeCa. HPV was detected by PCR and sequencing. Expression of HOX-positive cells was determined in each diagnostic group. RESULTS: Percentage of HOXB2- and HOXB13-positive cells gradually increased from means of 10.9% and 16.7%, respectively, in samples from healthy women, to 75.2% and 88.6% in those from CeCa patients. Frequency of HPV infection also increased from 13% in healthy tissue samples to 92.3% in CeCa. Both HOXB2 and HOXB13 proteins were preferentially expressed in HPV+ samples. CONCLUSIONS: The present study represents the first report on the expression of both HOXB2 and HOXB13 proteins through cervix tumorigenesis, providing evidence that increased expression of such proteins is a common event during progression to CeCa.
Asunto(s)
Cuello del Útero/metabolismo , Proteínas de Homeodominio/metabolismo , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/virología , Factores de Transcripción/metabolismo , Displasia del Cuello del Útero/patología , Neoplasias del Cuello Uterino/patología , Estudios de Casos y Controles , ADN Viral/genética , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Clasificación del Tumor , Estadificación de Neoplasias , Papillomaviridae/genética , Infecciones por Papillomavirus/metabolismo , Infecciones por Papillomavirus/patología , Reacción en Cadena de la Polimerasa , Pronóstico , Análisis de Matrices Tisulares , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/virología , Displasia del Cuello del Útero/metabolismo , Displasia del Cuello del Útero/virologíaRESUMEN
Composite pheochromocytomas (CP) account for only 3% of all pheochromocytomas. We analyzed the clinical, immunohistochemical, ultrastructural, DNA content, and 634 ret mutation features in a 56-year-old Mexican woman with CP localized in the right adrenal gland and associated to a blood pressure of 140/90 mmHg. Clinical symptoms were absent after surgery. The tumor showed pheochromocytoma and neuroblastoma components. This dual phenotype was supported by light microscopy and corroborated by immunohistochemistry and ultrastructural findings. Flow cytometric analysis showed that both components were diploid. A genetic mutational analysis of the ret oncogene in exon 11 showed no 634 mutation. This case demonstrates the indolent behavior of neuroblastoma associated to a sporadic-type CP in an adult patient.
Asunto(s)
Neoplasias de las Glándulas Suprarrenales/patología , ADN de Neoplasias/análisis , Proteínas de Drosophila , Neoplasias Primarias Secundarias/patología , Neuroblastoma/patología , Feocromocitoma/patología , Proteínas Proto-Oncogénicas/genética , Proteínas Tirosina Quinasas Receptoras/genética , Neoplasias de las Glándulas Suprarrenales/genética , Neoplasias de las Glándulas Suprarrenales/cirugía , Anciano , Biomarcadores de Tumor/análisis , Análisis Mutacional de ADN , Cartilla de ADN/química , Diploidia , Femenino , Citometría de Flujo , Humanos , Persona de Mediana Edad , Neoplasias Primarias Secundarias/genética , Neuroblastoma/genética , Neuroblastoma/cirugía , Feocromocitoma/genética , Feocromocitoma/cirugía , Reacción en Cadena de la Polimerasa , Proteínas Proto-Oncogénicas c-retRESUMEN
BACKGROUND: The invasive and metastatic potential of malignant cells results from complex interactions of numerous factors not yet fully understood. Genomic alterations such as ras overexpression and nm23-H1 inhibition have been found to be frequently associated with increased invasiveness in various cancers. On the other hand, secretion of different proteinases are necessary for malignant cells to traverse a network of matrix macromolecules, but the relationship between the genomic alterations and the proteolytic phenotype is still unclear. Our aim was to investigate whether the appearance of the proteolytic phenotype had any correlation with the expression of H-ras and nm23-H1 genes in carcinoma of the uterine cervix. METHODS: Twenty-five samples from patients with carcinoma of the uterine cervix at different clinical stages were studied. Cathepsin B1, plasminogen activator, and collagenase activity were assessed in tissue cytosols using specific synthetic oligopeptides as substrates. The expression of H-ras and nm23-H1 was investigated by means of immunohistochemistry and in situ hybridization. RESULTS: Our results showed that cathepsin B1 was the most consistently elevated proteinase, demonstrating a linear correlation with clinical staging. H-ras expression was found elevated in 40% of the cases. Nm23-H1 protein immunoreactivity was positive in 40% of the cases. No correlation was found among H-ras, cathepsin B1 activity, and survival rate. Among cases with high cysteine proteinase activity, a different clinical behavior depending on the expression of Nm23-H1 was observed. The cases with Nm23-H1 protein had a markedly better survival rate than those lacking this protein. In contrast, the absence of Nm23-H1 in association with high cathepsin B1 activity was a clear indicator of a poor prognosis. CONCLUSIONS: These findings suggest a complex interaction between the proteolytic phenotype and the expression of H-ras and nm23-H1 genes in carcinoma of the cervix that influences the clinical behavior of the tumor.
Asunto(s)
Carcinoma de Células Escamosas/genética , Regulación Neoplásica de la Expresión Génica , Genes ras , Proteínas de Unión al GTP Monoméricas/biosíntesis , Proteínas de Neoplasias/biosíntesis , Nucleósido-Difosfato Quinasa , Proteínas Proto-Oncogénicas p21(ras)/biosíntesis , Factores de Transcripción/biosíntesis , Neoplasias del Cuello Uterino/genética , Biomarcadores de Tumor/análisis , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Catepsina B/análisis , Colagenasas/análisis , Citosol/química , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Hibridación in Situ , Proteínas de Unión al GTP Monoméricas/genética , Nucleósido Difosfato Quinasas NM23 , Invasividad Neoplásica/genética , Proteínas de Neoplasias/genética , Estadificación de Neoplasias , Inhibidor 1 de Activador Plasminogénico/análisis , Factores de Transcripción/genética , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/patologíaRESUMEN
El virus de polioma es capaz de inducir tumores en sus hospederos naturales y transformar células en cultivo. Por otro lado, el virus de papiloma humano se ha relacionado con diversos tipos de neoplasias; de manera particular con lesiones anogenitales humanas. No se conoce con exactitud el mecanismo a través del cual estos virus inducen transformación y tumorigénesis. El presente trabajo muestra algunas de las características de los mecanismos que utilizan los virus mencionados para participar en la transformación y tumorigénesis. Además, se ha encontrado que ciertos aspectos de la infección por el virus de polioma son parecidos a la infección del virus del papiloma (ambos pertenecen a la misma familia Papovaviridae), por lo que se consideran algunas semejanzas y diferencias entre los mismos
Polyomavirus is able to induce tumors in its natural host as well as to transform cells in cultures. On the other hand, human papillomavirus has been involved in several types of neoplasias such as anogenital lesions. Little is known about the mechanisms through which these viruses induce both transformation and tumorigenesis. The present work shows some characteristics of the mechanisms that papillomavirus and polyomavirus use to participate in tumorigenesis. It has also been noticed that the infection caused by polyomavirus resembles that performed by papillomaviruses (which belong to the same Papovaviridae family). Some similarities and differences between these viruses are considered.
Asunto(s)
Papiloma/genética , Papiloma/virología , Neoplasias del Cuello Uterino/etiología , Neoplasias del Cuello Uterino/virología , Poliomavirus/genética , Transformación Celular Neoplásica , Virus Oncogénicos/genética , Integración ViralRESUMEN
Polyomavirus is able to induce tumors in its natural host as well as to transform cells in cultures. On the other hand, human papillomavirus has been involved in several types of neoplasias such as anogenital lesions. Little is known about the mechanisms through which these viruses induce both transformation and tumorigenesis. The present, work shows some characteristics of the mechanisms that papillomavirus and polyomavirus use to participate in tumorigenesis. It has also been noticed that the infection caused by polyomavirus resembles that performed by papillomaviruses (which belong to the same Papovaviridae family). Some similarities and differences between these viruses are considered.