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1.
Urol Oncol ; 41(12): 486.e15-486.e23, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37821306

RESUMEN

BACKGROUND: Advanced bladder squamous cell carcinoma (aBSCC) is an uncommon form of urinary bladder malignancy when compared with the much higher urothelial carcinoma incidence. We studied the genomic alteration (GA) landscape in a series of aBSCC based on the association with human papilloma virus (HPV) to determine if differences in GA would be observed between the positive and negative groups. METHODS: Using a hybrid capture-based FDA-approved CGP assay, a series of 171 aBSCC were sequenced to evaluate all classes of GA. Tumor mutational burden (TMB) was determined on up to 1.1 Mbp of sequenced DNA and microsatellite instability (MSI) was determined on up to 114 loci. Programmed cell death ligand -1 (PD-L1) expression was determined by IHC (Dako 22C3) with negative expression when PD-L1 was 0, lower expression of positivity set at 1 to 49%, and higher expression set at ≥50% expression. RESULTS: Overall, 11 (6.4%) of the aBSCC were found to harbor HPV sequences (10 HPV16 and 1 HPV 11). HPV+ status was identified slightly more often in women (NS) and in younger patients (P = 0.04); 2 female patients with aBSCC had a prior history of SCC including 1 anal SCC and 1 vaginal SCC. HPV+ aBSCC had fewer GA/tumor (P < 0.0001), more inactivating mutations in RB1 (P = 0.032), and fewer inactivating GA in CDKN2A (P < 0.0001), CDKN2B (P = 0.05), TERT promoter (P = 0.0004) and TP53 (P < 0.0001). GA in genes associated with urothelial carcinoma including FGFR2 and FGFR3 were similar in both HPV+ and HPV- aBSCC groups. MTAP loss (homozygous deletion) which has emerged as a biomarker for PRMT5 inhibitor-based clinical trials was not identified in any of the 11 HPV+ aBSCC cases, which was significantly lower than the 28% positive frequency of MTAP loss in the HPV- aBSCC group (P < 0.0001). MTOR and PIK3CA pathway GA were not significantly different in the 2 groups. Putative biomarkers associated with immunotherapy (IO) response, including MSI and TMB status, were also similar in the 2 groups. PD-L1 expression data was available for a subset of both HPV+ and HPV- cases and showed high frequencies of positive staining which was not different in the 2 groups. CONCLUSIONS: HPV+ aBSCC tends to occur more often in younger patients. As reported in other HPV-associated squamous cell carcinomas, HPV+ aBSCC demonstrates significantly reduced frequencies of inactivating mutations in cell cycle regulatory genes with similar GA in MTOR and PIK3CA pathways. The implication of HPV in the pathogenesis of bladder cancer remains unknown but warrants further exploration and clinical validation.


Asunto(s)
Carcinoma de Células Escamosas , Carcinoma de Células Transicionales , Infecciones por Papillomavirus , Neoplasias de la Vejiga Urinaria , Humanos , Femenino , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/complicaciones , Vejiga Urinaria/patología , Carcinoma de Células Transicionales/genética , Carcinoma de Células Transicionales/complicaciones , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/genética , Infecciones por Papillomavirus/epidemiología , Antígeno B7-H1/genética , Homocigoto , Eliminación de Secuencia , Carcinoma de Células Escamosas/patología , Genómica , Biomarcadores de Tumor/genética , Fosfatidilinositol 3-Quinasa Clase I/genética , Serina-Treonina Quinasas TOR/genética , Mutación , Proteína-Arginina N-Metiltransferasas/genética
2.
Transplant Proc ; 44(1): 72-4, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22310582

RESUMEN

BACKGROUND: Renal transplantation (RTx) is the best therapeutic modality for patient suffering from end-stage renal disease (ESRD) with positive pretransplantation hepatitis B surface antigen (HbsAg). We report 11 years of single-center experience on RTx vis-à-vis patient/graft survival, graft function in terms of serum creatinine (SCr), and rejection episodes in 35 ESRD patients with pretransplantation HbsAg positivity. PATIENTS AND METHODS: Thirty-five ESRD patients with pretransplantation HbsAg positivity underwent RTx at our center between 2000 and 2010. Mean recipient age was 36.06 ± 12.22 years; 30 were males and 5 were females. Mean donor age was 43.51 ± 13.63 years; 13 were males and 22 were females. The majority of donors were parents (31.42%) and spouses (22.85%). Mean HLA match was 2 ± 1.37. The most common recipient diseases leading to ESRD were chronic glomerulonephritis (51%) and diabetes (17.5%). Posttransplantation immunosuppression consisted of a calcineurin inhibitor-based regimen. RESULTS: Over mean follow-up of 6.16 ± 3.69 years, patient and graft survival rates were 71.42% and 71.42%, respectively, with mean SCr of 1.92 ± 0.62 mg% with 20% biopsy-proven acute rejection episodes. In total, 10 (28.57%) patients were lost, mainly to infections. CONCLUSION: RTx for ESRD with pretransplantation HbsAg positivity has acceptable graft function and patient/graft survival over 11 years follow-up and should be encouraged.


Asunto(s)
Antígenos de Superficie de la Hepatitis B/sangre , Hepatitis B/complicaciones , Fallo Renal Crónico/cirugía , Trasplante de Riñón , Adulto , Biomarcadores/sangre , Femenino , Rechazo de Injerto/etiología , Supervivencia de Injerto , Hepatitis B/diagnóstico , Hepatitis B/mortalidad , Humanos , Inmunosupresores/uso terapéutico , India , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/mortalidad , Trasplante de Riñón/efectos adversos , Trasplante de Riñón/mortalidad , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Análisis de Supervivencia , Factores de Tiempo , Resultado del Tratamiento , Adulto Joven
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