Vascular Endothelial Growth Factor (VEGF) Polymorphisms and Serum VEGF Levels in Women With Epithelial Ovarian Cancer, Benign Tumors, and Healthy Ovaries.

OBJECTIVE: This study analyzed the relation of 5 single-nucleotide polymorphisms (SNPs) in the VEGF (vascular endothelial growth factor) gene in patients with epithelial ovarian cancer (EOC), compared with patients carrying benign tumors or healthy ovaries. We studied serum VEGF levels and the relation with SNPs and association between VEGF SNPs and haplotypes with progression-free survival (PFS) in patients with cancer. METHODS: The genotyping of VEGF gene polymorphisms (-2578 C/A, -1154 G/A, -460 T/C, +405 G/C, +936 C/T) was performed in DNA isolated from blood samples of 100 women. The different genotypes were evaluated by quantitative real-time polymerase chain reaction. Vascular endothelial growth factor protein concentration was assessed in serum using solid-phase sandwich enzyme-linked immunosorbent assay. RESULTS: We found statistically significant differences in the distribution of VEGF genotypes among the 3 groups of patients: -2578 C/A between those with EOC and healthy ovary (P = 0.04), -460 T/C between those with EOC and healthy ovary (P = 0.03), and -460 T/C between those with benign tumors and healthy ovary (P = 0.02). Vascular endothelial growth factor serum levels were analyzed in patients with EOC. Higher levels were found in patients with clear cell carcinoma compared with those with serous, mucinous, or endometrioid tumors (P < 0.05). No clear association was observed between VEGF SNPs and serum VEGF levels. There was no significant correlation between VEGF SNPs and PFS. In haplotype analysis, CGTCT and CGTGT showed worse prognosis without reaching the statistical significance. CGCGC and AGTGC haplotypes had statistically significant differences among patients with EOC, benign tumors, and healthy ovaries (Ps = 0.046 and 0.041, respectively). CONCLUSIONS: The distribution of VEGF genotypes was different in patients with EOC, compared with those with benign tumors or women with healthy ovaries. Vascular endothelial growth factor serum levels were higher in patients with clear cell carcinoma. No correlation was found with improved PFS, but CGTCT and CGTGT haplotypes showed worse prognosis.

p16 gene methylation in colorectal cancer patients with long-term follow-up.

INTRODUCTION: p16 gene plays an important role in the cell cycle regulation and is considered an important tumor suppressor gene. Several mechanisms of gene inactivation have been described; in this study we have focused on p16 gene promoter methylation. In colorectal cancer p16 gene methylation is a frequent event. METHODS: 326 patients with sporadic colorectal cancer were included. DNA was extracted from tumor tissue samples obtained during the surgical procedure. Promoter methylation was analyzed using bisulfite modification and was detected by quantitative methylation-specific PCR. Frequency of p16 methylation was analyzed and compared with other clinicopathological variables. RESULTS: p16 gene methylation was detected in 24.8% of patients. Methylation was associated with differentiation grade and with tumor location: methylation was frequent in poorly differentiated tumors and had low frequency in distal colon. The p16 promoter methylation discriminated a subgroup of patients with better prognosis in poorly differentiated tumors. CONCLUSIONS: p16 methylation was a frequent event in our population and was able to induce differences in the overall survival of patients with poorly differentiated tumors.

Metilación de p16 en pacientes intervenidos de cáncer colorrectal tras un largo periodo de seguimiento / p16 gene methylation in colorectal cancer patients with long-term follow-up

Introducción: el gen p16 está implicado en la regulación del ciclo celular y se considera un importante gen supresor de tumores. Objetivos: se han descrito diferentes mecanismos de inactivación génica, en este estudio nos hemos centrado en la metilación del promotor del gen p16. En el cáncer colorrectal la metilación de p16 es una alteración frecuente. Material y métodos: se incluyeron 326 pacientes con cáncer colorrectal esporádico. El ADN se extrajo de muestras tumorales obtenidas durante la cirugía. La metilación del promotor se analizó mediante un proceso de modificación con bisulfito y posterior PCR cuantitativa especifica para metilación. Se analizó la frecuencia de la metilación de p16 y se comparó con las variables clinicopatológicas. Resultados: la metilación del gen p16 se detectó en el 24,8% de los pacientes. La metilación de p16 se relacionó con el grado de diferenciación y con la localización tumoral: la metilación fue mas frecuente en los tumores pobremente diferenciados y tuvo una baja frecuencia en el colon distal. La metilación del promotor de p16 discrimina un subgrupo de pacientes con mejor pronóstico en los tumores pobremente diferenciados. Conclusiones: la metilación de p16 es un evento frecuente en nuestra población y es capaz de inducir diferencias en la supervivencia global de los pacientes con tumores moderadamente diferenciados(AU)

Introduction: p16 gene plays an important role in the cell cycle regulation and is considered an important tumor suppressor gene. Several mechanisms of gene inactivation have been described; in this study we have focused on p16 gene promoter methylation. In colorectal cancer p16 gene methylation is a frequent event. Methods: 326 patients with sporadic colorectal cancer were included. DNA was extracted from tumor tissue samples obtained during the surgical procedure. Promoter methylation was analyzed using bisulfite modification and was detected by quantitative methylation- specific PCR. Frequency of p16 methylation was analyzed and compared with other clinicopathological variables. Results: p16 gene methylation was detected in 24,8% of patients. Methylation was associated with differentiation grade and with tumor location: methylation was frequent in poorly differentiated tumors and had low frequency in distal colon. The p16 promoter methylation discriminated a subgroup of patients with better prognosis in poorly differentiated tumors. Conclusions: p16 methylation was a frequent event in our population and was able to induce differences in the overall survival of patients with poorly differentiated tumors(AU)

Actualidad y futuro en las técnicas de cuantificiación de células tumorales circulantes: su importancia en tumores sólidos epiteliales / Current and future techniques for quantifying circulating tumor cells: importance in solid epithelial tumors

Las metástasis de los tumores sólido se producen cuando las células de un carcinoma primario o metastásico migran en el sistema circulatorio y proliferan en lugares distantes del organismo. Los carcinomas son de origen epithelial, y no es habitual que estas células se encuentren en el torrente circulatorio. La presencia de células tumorales circulantes (CTC) en sangre periférica detectadas con CellSearch(R) Circulating Tumor Cell System, está asociada a menor supervivencia libre de enfermedad (SLE) y menor supervivencia global (SG) en pacientes de cáncer de mama, colorrectal y de próstata metastatizante. Esta prueba sirve para ayudar en la monitorización de pacientes con cáncer de mama, colorrectal o próstata. Además, en el presente artículo revisamos otras técnicas de detección de células tumorales circulantes y su aplicabilidad (AU)

Cancer metastasis occurs when cells shed from a primary or metastatic tumor, enter the circulation, and begin to grow in distant locations of the body. Carcinomas are derived from epithelial cells that are not normally found in circulation. The presence of circulating tumor cells (CTC) in the peripheral blood, as detected by the CellSearch(R) Circulating Tumor Cell Kit, is associated with disease free survival and decreased overall survival in patients treated for metastatic breast, colorectal or prostate cancer. The test is to be used as an aid in the monitoring of patients with metastatic breast, colorectal or prostate cancer. In our article we will evaluate other methods of analysing circulating tumor cells and their clinical application (AU)