GBX2 Methylation Is a Novel Prognostic Biomarker and Improves Prediction of Biochemical Recurrence Among Patients with Prostate Cancer Negative for Intraductal Carcinoma and Cribriform Architecture.

BACKGROUND: Tumor intraductal carcinoma/cribriform architecture (IDC/C) is associated with an unfavorable prognosis and biochemical recurrence (BCR) in prostate cancer (PCa). Up to 70% of PCa patients are IDC/C-negative, but it is estimated that 20% of these cases still experience BCR. Thus, biomarkers for better detection of aggressive disease in IDC/C-negative patients are required. OBJECTIVE: To investigate tumor-specific methylation of the transcription factor GBX2 as a novel prognosticator and predictor of BCR in PCa patients stratified by histopathologic features including IDC/C. DESIGN, SETTING, AND PARTICIPANTS: Using genome-wide methylome profiling, we identified higher GBX2 methylation in grade group (GG) 4 tumors compared to GG1 (discovery cohort). The prognostic nature of GBX2 methylation was validated in silico using The Cancer Genome Atlas data (n=478) and a quantitative methylation assay for radical prostatectomy samples (n=254). Regulation of GBX2 methylation was investigated in prostate cells using methyl-CpG-binding domain sequencing and methylation analysis in functional knockouts of TET2, a key epigenetic player in prostate carcinogenesis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The association of GBX2 methylation with Gleason score (GS), pathologic stage (pT), IDC/C, and BCR was analyzed using Kruskal-Wallis and Mann-Whitney tests. Univariate and multivariate Cox regression analyses were used to predict BCR. RESULTS: GBX2 methylation was associated with GS (p<0.05), pT (p<0.01), and BCR (p<0.05). GBX2 methylation (p=0.004), GS (p<0.001), pT (p=0.012), and prostate-specific antigen (p=0.005) were independent predictors of BCR. Among IDC/C-negative patients, GBX2 methylation improved prediction of BCR (p=0.002). Loss of TET2 in prostate cells resulted in greater GBX2 methylation. CONCLUSIONS: We identified GBX2 methylation as a novel prognostic factor in PCa and an independent predictor of BCR. We demonstrated the additive value of GBX2 methylation in predicting BCR among IDC/C-negative patients and elucidated a novel TET2-mediated upstream epigenetic regulatory mechanism of GBX2. PATIENT SUMMARY: We identified GBX2 methylation as a promising prognostic biomarker that could improve the identification of prostate cancer patients at higher risk of biochemical recurrence.

Tumores mucinosos del páncreas / Mucinous tumors of the pancreas

Los tumores mucinosos del páncreas son lesiones premalignas que cursan casi siempre de forma asintomática y la mayoría de las veces se realiza su detección de forma incidental. Tanto el diagnóstico como la conducta terapéutica constituyen un reto para las diferentes especialidades involucradas en el manejo de estas lesiones, dadas las diferencias en la historia natural del espectro de las lesiones: benignas, malignas y borderline; de ahí la importancia de los esfuerzos por lograr consensuar criterios en aras de un mejor seguimiento. Interesados por estos elementos se decide realizar esta revisión bibliográfica de los tumores mucinosos del páncreas e identificar los criterios para el diagnóstico y la conducta a seguir. Para lograr este objetivo se revisó la bibliografía más actualizada consultando revistas digitales, impresas y temas obtenidos de diferentes sitios Web, incluyendo la guía del consenso internacional para el manejo de los tumores mucinosos pancreáticos (AU)

Mucinous tumors of the pancreas are premalignant lesions that occur almost always asymptomatic and most of the time they are detected incidentally. Both the diagnosis and therapeutic behavior constitute a challenge for the different specialties involved in the management of these lesions, given the differences in the natural history of the spectrum of lesions: benign, malignant and borderline; hence the importance of efforts to achieve consensus criteria in order to better monitoring. The authors were interested in these items, so it was decided to conduct this bibliographic review on mucinous tumors of the pancreas and to identify the criteria for diagnosis and behavior to follow. To achieve this goal the most updated bibliography was reviewed, it was consulted digital journals, printed ones and themes obtained from different Web sites, including the international consensus guidelines for management of pancreatic mucinous tumors (AU)