Recurrent lymphangiomyomatosis after transplantation: genetic analyses reveal a metastatic mechanism.

Karbowniczek, Magdalena; Astrinidis, Aristotelis; Balsara, Binaifer R; Testa, Joseph R; Lium, James H; Colby, Thomas V; McCormack, Francis X; Henske, Elizabeth Petri

Karbowniczek, Magdalena; Astrinidis, Aristotelis; Balsara, Binaifer R; Testa, Joseph R; Lium, James H; Colby, Thomas V; McCormack, Francis X; Henske, Elizabeth Petri.

Afiliación

Karbowniczek M; Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111, USA.

Am J Respir Crit Care Med ; 167(7): 976-82, 2003 Apr 01.

Article en En | MEDLINE | ID: mdl-12411287

RESUMEN

Lymphangiomyomatosis (LAM) is characterized by the proliferation of abnormal smooth muscle cells and cystic degeneration of the lung. LAM affects almost exclusively young women. Although lung transplantation provides effective therapy for end-stage LAM, there are reports of LAM recurrence after lung transplantation. Whether these recurrent LAM cells arise from the patient or the lung transplant donor is an area of controversy. We used microsatellite marker fingerprinting and TSC2 gene mutational analysis to study a patient with recurrent LAM after single-lung transplantation. The DNA microsatellite marker pattern indicated the presence of patient-derived LAM cells in the allograft. A somatic one base pair deletion in exon 18 of the TSC2 gene was identified in pulmonary and lymph node LAM cells before transplantation. The same mutation was in the recurrent LAM, demonstrating that the recurrent LAM was derived from the patient. Fluorescence in situ hybridization revealed that cells immunoreactive with the monoclonal antibody HMB-45 did not contain a Y chromosome. These data indicate that histologically benign LAM cells can migrate or metastasize in vivo to the transplanted lung. In addition, the patient had no evidence of a renal angiomyolipoma at autopsy and therefore demonstrated for the first time that somatic TSC2 mutations cause LAM in patients without angiomyolipomas.

Asunto(s)

Neoplasias Pulmonares/cirugía; Trasplante de Pulmón; Linfangioleiomiomatosis/cirugía; Recurrencia Local de Neoplasia/etiología; Adulto; Alelos; Secuencia de Bases; Biomarcadores de Tumor/genética; Biopsia; Cromosomas Humanos Par 16/genética; Cromosomas Humanos Y/genética; ADN de Neoplasias/genética; Exones/genética; Femenino; Genes Supresores de Tumor; Heterocigoto; Humanos; Pérdida de Heterocigocidad/genética; Pulmón; Neoplasias Pulmonares/genética; Neoplasias Pulmonares/secundario; Ganglios Linfáticos; Linfangioleiomiomatosis/genética; Linfangioleiomiomatosis/patología; Repeticiones de Microsatélite/genética; Recurrencia Local de Neoplasia/genética; Recurrencia Local de Neoplasia/secundario; Complicaciones Posoperatorias/etiología; Proteínas Represoras/genética; Insuficiencia del Tratamiento; Proteína 2 del Complejo de la Esclerosis Tuberosa; Proteínas Supresoras de Tumor

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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trasplante de Pulmón / Linfangioleiomiomatosis / Neoplasias Pulmonares / Recurrencia Local de Neoplasia Tipo de estudio: Etiology_studies / Prognostic_studies Límite: Adult / Female / Humans Idioma: En Revista: Am J Respir Crit Care Med Asunto de la revista: TERAPIA INTENSIVA Año: 2003 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

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