RESUMEN
Cancer is now the most severe complication in the long term in transplant recipients. As most solid-organ or hematopoietic stem-cell transplantations are allogeneic, chimerism studies can be performed on cancers occurring in recipients. We summarize here the different methods used to study chimerism in cancers developing in allogeneic-transplant recipients, analyze their respective advantages and report the main results obtained from these studies. Chimerism analyses of cancers in transplant recipients require methods suited to tissue samples. In the case of gender-mismatched transplantation, the XY chromosomes can be explored using fluorescent in situ hybridization on whole-tissue sections or Y-sequence-specific PCR after the laser microdissection of tumor cells. For cancers occurring after gender-matched transplantation, laser microdissection of tumor cells enables studies of microsatellite markers and high-resolution melting analysis of mitochondrial DNA on genes with marked polymorphism, provided these are different in the donor and the recipient. The results of different studies address the cancers that develop in both recipients and in transplants. The presence of chimeric cells in these two types of cancer implies an exchange of progenitor/stem-cells between transplant and recipient, and the plasticity of these progenitor/stem-cells contributes to epithelial cancers. The presence of chimeric cells in concomitant cancers and preneoplastic lesions implies that the oncogenesis of these cancers progresses through a multistep process.
Asunto(s)
Quimerismo , Neoplasias Glandulares y Epiteliales/genética , Receptores de Trasplantes , ADN Mitocondrial/genética , Femenino , Humanos , Masculino , Repeticiones de Microsatélite/genética , Trasplante HomólogoRESUMEN
Tumor cells with donor genotype have been identified in human skin cancer after allogeneic transplantation; however, the donor contribution to the malignant epithelium has not been established. Kidney transplant recipients have an increased risk of invasive skin squamous cell carcinoma (SCC), which is associated with accumulation of the tumor suppressor p53 and TP53 mutations. In 21 skin SCCs from kidney transplant recipients, we systematically assessed p53 expression and donor/recipient origin in laser-microdissected p53+ tumor cells. In one patient, molecular analyses demonstrated that skin tumor cells had the donor genotype and harbored a TP53 mutation in codon 175. In a kidney graft biopsy performed 7 years before the skin SCC diagnosis, we found p53+ cells in the renal tubules. We identified the same TP53 mutation in these p53+ epithelial cells from the kidney transplant. These findings provide evidence for a donor epithelial cell contribution to the malignant skin epithelium in the recipient in the setting of allogeneic kidney transplantation. This finding has theoretical implications for cancer initiation and progression and clinical implications in the context of prolonged immunosuppression and longer survival of kidney transplant patients.
Asunto(s)
Carcinoma de Células Escamosas/etiología , Trasplante de Riñón/efectos adversos , Neoplasias Cutáneas/etiología , Sustitución de Aminoácidos , Secuencia de Bases , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Análisis Mutacional de ADN , ADN Mitocondrial/genética , Células Epiteliales/metabolismo , Humanos , Trasplante de Riñón/patología , Túbulos Renales/patología , Captura por Microdisección con Láser , Repeticiones de Microsatélite , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patología , Trasplante Homólogo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismoAsunto(s)
Hemangioblastoma/patología , Neoplasias Renales/patología , Angiomiolipoma/diagnóstico , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Renales/diagnóstico , Diagnóstico Diferencial , Granuloma Piogénico/diagnóstico , Hemangioblastoma/metabolismo , Hemangioblastoma/cirugía , Hemangiopericitoma/diagnóstico , Humanos , Neoplasias Renales/metabolismo , Neoplasias Renales/cirugía , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Intracystic papillary carcinoma (IPC), a breast tumor mainly occuring in the elderly, has long been considered as a variant of ductal carcinoma in situ (DCIS). This is now debated since metastatic cases have been reported. In this study, surgical pieces of 20 IPCs were reassessed, and markers of myopepithelial layer (p63, CD10 and Smooth Muscle Actin) as well as estrogen receptors (ER) and progesterone receptors (PgR) and C-erb-B2 oncoprotein expression were systematically performed and quantified. In 10 cases, an associated unequivocal invasive component was found. In all 20 cases, no myoepithelial layer was found. Eighteen tumors were ER positive, 14 were PgR positive. Moreover, none of the tumors over-expressed C-erb-B2 oncoprotein. Therefore this study showed that in all cases of IPC there were microscopic features of invasive carcinoma despite good clinical prognostic indicators, and that precise characterization of tumors requires extensive paraffin embedding of surgical pieces.
Asunto(s)
Neoplasias de la Mama/patología , Carcinoma Intraductal no Infiltrante/patología , Carcinoma Papilar/patología , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/química , Carcinoma Intraductal no Infiltrante/química , Carcinoma Papilar/química , Femenino , Humanos , Inmunohistoquímica , Mamografía , Proteínas de la Membrana/análisis , Persona de Mediana Edad , Receptor ErbB-2/análisisRESUMEN
Microscopic colitis is the most common cause of chronic watery diarrhea, with normal mucosal appearance during colonoscopy. The diagnosis is made by pathological examination of biopsy specimens showing colitis with normal architecture of the mucosa. The two most frequent forms of microscopic colitis are lymphocytic colitis and collagenous colitis, but other atypical variants have been described. We report a case of lymphocytic colitis with multinucleated large cells and we discuss a variant of giant cells microscopic colitis.