RESUMEN
We analyzed the incidence, clinicopathological features, risk factors and prognosis of patients with EBV-associated post-transplant lymphoproliferative disorder (EBV-PTLD) in 288 adults undergoing umbilical cord blood transplantation (UCBT) at a single institution. Twelve patients developed proven EBV-PTLD at a median time of 73 days (range, 36-812). Three-year cumulative incidence (CI) of EBV-PTLD was 4.3% (95% CI: 1.9-6.7). All patients presented with extranodal involvement. Most frequently affected sites were the liver, spleen, central nervous system (CNS), Waldeyer's ring and BM in 7, 6, 4, 3 and 3 patients, respectively. One patient had polymorphic and 11 had monomorphic EBV-PTLD (7 diffuse large B-cell lymphomas not otherwise specified, 4 plasmablastic lymphomas). We confirmed donor origin and EBV infection in all histological samples. EBV-PTLD was the cause of death in 11 patients at a median time of 23 days (range, 1-84). The 3-year CI of EBV-PTLD was 12.9% (95% CI: 3.2-22.5) and 2.6% (95% CI: 0.5-4.7) for patients receiving reduced-intensity conditioning (RIC) and myeloablative conditioning, respectively (P<0.0001). In conclusion, adults with EBV-PTLD after UCBT showed frequent visceral and CNS involvement. The prognosis was poor despite routine viral monitoring and early intervention. An increased risk of EBV-PTLD was noted among recipients of RIC regimens.
Asunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical/efectos adversos , Infecciones por Virus de Epstein-Barr/complicaciones , Enfermedades Hematológicas/fisiopatología , Enfermedades Hematológicas/terapia , Trastornos Linfoproliferativos/virología , Adolescente , Adulto , Anciano , Sistema Nervioso Central/patología , Femenino , Enfermedad Injerto contra Huésped , Herpesvirus Humano 4 , Humanos , Incidencia , Hígado/patología , Trastornos Linfoproliferativos/etiología , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Bazo/patología , Factores de Tiempo , Acondicionamiento Pretrasplante , Adulto JovenAsunto(s)
Enfermedades del Ciego/diagnóstico , Enfermedades del Ciego/parasitología , Parasitosis Intestinales/diagnóstico , Tricuriasis/diagnóstico , Anemia/parasitología , Enfermedades del Ciego/complicaciones , Femenino , Hemorragia Gastrointestinal/parasitología , Humanos , Parasitosis Intestinales/complicaciones , Persona de Mediana Edad , Prurito/parasitología , Tricuriasis/complicacionesAsunto(s)
Síndrome Inflamatorio de Reconstitución Inmune/diagnóstico , Sarcoidosis/diagnóstico , Enfermedades de la Piel/diagnóstico , Adulto , Terapia Antirretroviral Altamente Activa/efectos adversos , Femenino , Infecciones por VIH/tratamiento farmacológico , Humanos , Sarcoidosis Pulmonar/diagnóstico , Factores de TiempoRESUMEN
BACKGROUND: Activated leucocyte cell adhesion molecule (ALCAM, CD166) is a cell surface member of the immunoglobulin superfamily. ALCAM expression has prognostic relevance in prostate and colon cancer. OBJECTIVE: To evaluate ALCAM protein expression in breast cancer by immunohistochemistry and to correlate expression levels with clinicopathological data. METHODS: 162 primary breast carcinomas with a mean clinical follow up time of 53 months were immunostained using a monoclonal ALCAM antibody. The staining was evaluated as an immunoreactive score (IRS) and grouped into low v high for both membranous and cytoplasmic staining. RESULTS: Intraductal and invasive carcinomas showed a higher ALCAM expression (median IRS 4 and 6 respectively) than normal breast tissue (IRS 2). In univariate survival analyses a significant association of high cytoplasmic ALCAM expression with shortened patient disease-free survival (mean (SD) five year non-progression rate, 69.4 (4.6)% v 49.4 (11.1)%, p = 0.0142) was found. In multivariate analyses of disease-free survival times, high cytoplasmic ALCAM expression (relative risk (RR) = 2.086, p = 0.026) and nodal status (RR = 2.246, p = 0.035) were significantly associated with earlier disease progression, whereas tumour grading (RR = 1.6, p = 0.052) was of borderline significance. CONCLUSIONS: The data suggest that strong cytoplasmic ALCAM expression in primary breast cancer, as detected by immunohistochemistry, might be a new marker for a more aggressive breast cancer biology.
Asunto(s)
Molécula de Adhesión Celular del Leucocito Activado/análisis , Biomarcadores de Tumor/análisis , Neoplasias de la Mama/química , Carcinoma Ductal de Mama/química , Citoplasma/química , Adulto , Anciano , Anciano de 80 o más Años , Mama/química , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/mortalidad , Carcinoma Ductal de Mama/patología , Estudios de Casos y Controles , Membrana Celular/química , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica/métodos , Metástasis Linfática , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Pronóstico , Tasa de SupervivenciaRESUMEN
Human kallikrein 14 (KLK14) is a steroid hormone-regulated member of the tissue kallikrein family of serine proteases, for which a prognostic and diagnostic value in breast cancer has been suggested. To further characterise the value of KLK14 as a breast tumour marker, we have carefully analysed KLK14 expression in normal breast tissue and breast cancer both on the RNA level by real-time RT-PCR (n = 39), and on the protein level (n = 127) using a KLK14-specific antibody for immunohistochemistry. We correlated KLK14 protein expression data with available clinico-pathological parameters (mean follow-up time was 55 months) including patient prognosis. KLK14 RNA expression as quantified by real-time RT-PCR was significantly more abundant in breast tumours compared to normal breast tissue (P = 0.027), an issue that had not been clarified recently. Concordantly with the RNA data, cytoplasmic KLK14 protein expression was significantly higher in invasive breast carcinomas compared to normal breast tissues (P = 0.003). Furthermore, KLK14 protein expression was associated with higher tumour grade (P = 0.041) and positive nodal status (P = 0.045) but was not significantly associated with shortened disease-free or overall patient survival time in univariate analyses. We conclude that KLK14 is clearly overexpressed in breast cancer in comparison to normal breast tissues and is positively associated with conventional parameters of tumour aggressiveness, but due to a missing association with survival times, the use of KLK14 immunohistochemistry as a prognostic marker in breast cancer is questionable.