RESUMEN
Melanocytic lesions in certain locations (eg, genital, breast, acral) may have histologic and clinical features simulating melanoma. Here we describe a group of lesions from the lower distal extremity and analyze their histologic features and possible relation to dysplastic nevi (DN) and melanomas. One hundred fifteen melanocytic lesions from the ankle were retrieved from January 1990 to August 2006 from the files of M. D. Anderson Cancer Center and were classified as benign melanocytic nevi (BN; n=17), DN (n=35), melanomas (MM; n=52), and melanocytic nevi of the ankle with atypical features (MNAAF; ie, cases that did not readily fit in any of the previous categories, n=11). Data analyzed included clinical (age and sex) and histologic features (circumscription, symmetry, cohesiveness of nests, suprabasal melanocytes, confluence, single-cell proliferation, nuclear chromasia, size, and nucleolar features). Follow-up was collected for all MNAAF. MNAAF differ from the other types of lesions in regard to sex incidence (73% in women). The median age of those patients MNAAF was 47 years (range 29 to 76 y). All MNAAF showed moderate-severe architectural disorder whereas 78% showed only mild-moderate cytologic atypia. No MNAAF cases had recurred after follow-up (4 mo to 13 y). This study highlights a group of melanocytic lesions located on the ankle that share histologic features with acral nevi, DN, and melanoma. These lesions are more predominant in females and have moderate to severe architectural atypia but only mild-moderate cytologic atypia. After complete excision, follow-up data indicate an apparently benign outcome. Pathologists should be aware of this type of lesions to avoid overdiagnosis of melanoma.
Asunto(s)
Errores Diagnósticos/prevención & control , Síndrome del Nevo Displásico/patología , Peca Melanótica de Hutchinson/patología , Nevo Pigmentado/patología , Lesiones Precancerosas/patología , Neoplasias Cutáneas/patología , Adulto , Anciano , Anciano de 80 o más Años , Tobillo , Biomarcadores de Tumor/metabolismo , Diagnóstico Diferencial , Síndrome del Nevo Displásico/metabolismo , Femenino , Humanos , Peca Melanótica de Hutchinson/metabolismo , Masculino , Melaninas/metabolismo , Persona de Mediana Edad , Nevo Pigmentado/metabolismo , Lesiones Precancerosas/metabolismo , Estudios Retrospectivos , Neoplasias Cutáneas/metabolismoRESUMEN
Human soft tissue sarcoma (STS) is a highly lethal malignancy in which control of metastasis determines survival. Little is known about the molecular determinants of STS dissemination. Here, we show that human STS express high levels of matrix metalloproteinase-9 (MMP-9) and that MMP-9 expression levels correlate with sequence analysis-defined p53 mutational status. Reintroduction of wild-type p53 (wtp53) into mutant p53 STS cell lines decreased MMP-9 mRNA and protein levels, decreased zymography-assessed MMP-9 proteolytic activity, and decreased tumor cell invasiveness. Reintroduction of wtp53 into STS xenografts decreased tumor growth and MMP-9 protein expression. Luciferase reporter studies showed that reintroduction of wtp53 into mutant p53 STS cells decreased MMP-9 promoter activity. Deletion constructs of the MMP-9 promoter identified a region containing a p53-responsive element that lacked a p53 consensus binding site but did contain a nuclear factor-kappaB (NF-kappaB) site. Mutating this NF-kappaB binding site eliminated the wtp53-repressive effect. Electrophoretic mobility shift assays confirmed decreased NF-kappaB binding in STS cells in the presence of wtp53. Our findings suggest a role for MMP-9 in STS progression and expand the role of p53 in molecular control of STS growth and metastasis. Therapeutic interventions in human STS targeting MMP-9 activity directly or via reintroduction of wtp53 merit further investigation.