Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 3 de 3
Filtrar
1.
Mod Pathol ; 23(3): 404-12, 2010 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-20062014

RESUMEN

Differentiated vulvar intraepithelial neoplasia is a unique precursor to vulvar squamous cell carcinoma that is typically HPV-negative and frequently associated with nuclear p53 staining. These features imply a mode of pathogenesis involving somatic mutations. However, the genetic relationship of differentiated vulvar intraepithelial neoplasm and vulvar squamous cell carcinoma and the role of Tp53 mutations in this process have not been resolved. We analyzed 11 differentiated vulvar intraepithelial neoplasms and 6 associated vulvar squamous cell carcinomas. Sections were stained for p53 and p63 and DNA from multiple epithelial sites, representing normal control tissues (n=10), differentiated vulvar intraepithelial neoplasias (n=18), and vulvar squamous cell carcinomas (n=6), were obtained by laser capture microdissection, and sequenced for exons 2-11 of Tp53. Six of 10 cases contained at least one Tp53 mutation-positive differentiated vulvar intraepithelial neoplasia focus; 4 strongly p53 immuno-positive and 2 negative. Staining for p53 and p63 co-localized, targeting the immature epithelium, but surface epithelium was Tp53 mutation-positive. Four of five vulvar squamous cell carcinomas were Tp53 mutation-positive; two shared identical Tp53 mutation with adjacent differentiated vulvar intraepithelial neoplasia. Disparate foci of differentiated vulvar intraepithelial neoplasia often showed different mutations consistent with multiple neoplastic clones. Differentiated vulvar intraepithelial neoplasia is, with few exceptions, associated with Tp53 mutations and will be p53 immunopositive when missense mutations (versus some nonsense and all deletion mutations) are present. Multiple Tp53 mutations in different sites supports the presence of multiple independent genetic events, but shared Tp53 mutations in both differentiated vulvar intraepithelial neoplasia and vulvar squamous cell carcinoma support a genetic relationship between the two. The confinement of p53 staining to immature cell nuclei is consistent with maturation-dependent degradation of mutant p53 protein.


Asunto(s)
Carcinoma in Situ/genética , Carcinoma de Células Escamosas/genética , Mutación , Proteína p53 Supresora de Tumor/genética , Neoplasias de la Vulva/genética , Carcinoma in Situ/patología , Carcinoma de Células Escamosas/patología , Núcleo Celular/metabolismo , Núcleo Celular/patología , Femenino , Humanos , Técnicas para Inmunoenzimas , Microdisección , Neoplasias Primarias Múltiples , Proteína p53 Supresora de Tumor/metabolismo , Neoplasias de la Vulva/patología
2.
Mod Pathol ; 21(9): 1067-74, 2008 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-18552822

RESUMEN

Topoisomerase IIalpha and minichromosome maintenance protein 2 are proteins associated with aberrant S-phase induction. The current study evaluated the performance of these biomarkers (ProEx C; TriPath Oncology, Burlington, NC) compared with p16(INK4A) and MiB-1 in distinguishing high-grade squamous intraepithelial lesions (HSILs) from HSIL mimics. We collected archival cervical biopsy, cone, and curettage specimens from 96 cases in which the differential diagnosis of HSIL vs reactive epithelial changes was considered. Hematoxylin- and eosin-stained slides were reviewed independently by three pathologists and scored for the presence or absence of SIL. Immunostains for ProEx C, p16, and MiB-1 were available for 95, 96, and 59 samples, respectively, and classified blinded to histological interpretation. Strong nuclear and cytoplasmic staining for p16 and staining for MiB-1 and ProEx C that extended beyond the lower one-third of the epithelium were scored as positive. Chi(2)-tests and receiver operating characteristic analysis were conducted to statistically compare biomarker immunostaining performance against majority histological interpretation of SIL. Agreement between pathologists was also assessed by the kappa-statistic. Inter-observer agreement ranged from fair to moderate (kappa=0.37-0.57). All three biomarkers correlated strongly with the majority diagnosis of SIL (P<0.001). Positive staining for ProEx C, p16, and MiB-1 was observed in 87% (N=52/60), 84% (N=51/61), and 94% (34/36), respectively, of SIL and negative in 71% (N=25/35), 63% (N=22/35), and 52% (N=12/23), respectively, of majority diagnoses of NoSIL. The combination of p16/ProEx C predicted more SIL (92%, N=33/36) and NoSIL (61%, N=14/23) than p16 plus MiB-1 (94%, N=34/36 and 43%, N=10/23), although this difference was not statistically significant. ProEx C appears to provide an equivalent level of sensitivity and a higher level of specificity for HSIL alone or in conjunction with p16. Its principal value may be in providing a lower false positive rate for NoSIL relative to MiB-1.


Asunto(s)
Antígenos de Neoplasias/análisis , Biomarcadores de Tumor/análisis , Proteínas de Ciclo Celular/análisis , Inhibidor p16 de la Quinasa Dependiente de Ciclina/análisis , ADN-Topoisomerasas de Tipo II/análisis , Proteínas de Unión al ADN/análisis , Proteínas Nucleares/análisis , Ubiquitina-Proteína Ligasas/análisis , Displasia del Cuello del Útero/química , Neoplasias del Cuello Uterino/química , Atrofia/diagnóstico , Núcleo Celular/química , Núcleo Celular/patología , Cuello del Útero/patología , Citoplasma/química , Citoplasma/patología , Diagnóstico Diferencial , Femenino , Humanos , Metaplasia , Componente 2 del Complejo de Mantenimiento de Minicromosoma , Curva ROC , Neoplasias del Cuello Uterino/patología , Displasia del Cuello del Útero/patología
3.
Gynecol Oncol ; 92(3): 856-65, 2004 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-14984953

RESUMEN

OBJECTIVE: The present study investigates the influence of lymph node pathological features and HPV DNA status on the prognosis of vulvar invasive tumors. METHODS: This study includes 184 consecutive cases of primary invasive squamous cell carcinoma of the vulva treated by radical surgery from 1975 to 1992, in São Paulo, Brazil. Clinical follow-up data was collected from patient files and hematoxilin-eosin sections were reviewed. HPV detection and typing was done by polymerase chain reaction (PCR), using specific and generic primers, followed by dot blot hybridization (DBH) with type-specific oligonucleotide probes for 19 HPV types. Age-adjusted Kaplan-Meier survival curves and Cox proportional hazards models were used to analyze the cancer risk associations for all DNA and pathology-related variables. RESULTS: Among 161 cases tested by PCR, 38 (23.6%) were positive for high-risk HPV types. Regional lymph nodes of 43 cases, including all those of HPV-positive tumors and a sample of the ones removed from patients with HPV negative tumors, were evaluated by the same method. HPV DNA was found in the lymph nodes of 10 cases. In every case, at least one lymph node was metastatic and the HPV detected in the lymph nodes were of the same type as those found in the primary tumor in all cases. Multivariate analysis including age, race, pattern of invasion, tumor thickness, inflammatory reaction, surgical margins, number of node metastases, presence of extracapsular growth, depth of invasion, and presence of high-risk HPV DNA was performed. Following automated selections of this model, node variables important for prognosis that remained were number of node metastases and presence of extracapsular growth. CONCLUSIONS: Patients with four or more node metastases associated with extracapsular spread were 5.6 (95%CI: 2.3-13.1) times more likely to die from cancer and 10.0 (95%CI: 4.0-24.9) times more likely to have a recurrence than patients without metastases. The HPV status in the tumor was not important as a prognostic factor.


Asunto(s)
Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/virología , ADN Viral/análisis , Ganglios Linfáticos/patología , Papillomaviridae/genética , Neoplasias de la Vulva/patología , Neoplasias de la Vulva/virología , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/cirugía , Estudios de Cohortes , Supervivencia sin Enfermedad , Femenino , Humanos , Ganglios Linfáticos/virología , Metástasis Linfática , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/virología , Infecciones por Papillomavirus/genética , Estudios Retrospectivos , Infecciones Tumorales por Virus/genética , Neoplasias de la Vulva/cirugía
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA