Effects of caspase-9 and survivin gene polymorphisms in pancreatic cancer risk and tumor characteristics.

OBJECTIVES: This case-control study was performed to evaluate the association between a specific caspase-9 polymorphism as well as the genetic polymorphism -31G/C located in the cycle-dependent elements/cell cycle homology regions repressor element of the human survivin promoter and the risk of pancreatic cancer. METHODS: Eighty patients with pancreatic cancer and 160 healthy controls were investigated for genotype and allelic frequencies of caspase-9 1263A/G and survivin -31G/C polymorphisms by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism. RESULTS: The G carrier group of patients and the G allele of caspase-9 1263A/G were overrepresented among the pancreatic cancer cases. With regard to tumor characteristics, a statistically significant association was detected between the survivin C carrier group of patients and the advanced T stage as well as the presence of lymph node metastasis. CONCLUSIONS: The caspase-9 G allele confers increased susceptibility to pancreatic cancer development, and the survivin C carriage status may be related to aggressive features of this malignancy.

Prospective evaluation of sexual function after open and laparoscopic surgery for rectal cancer.

BACKGROUND: Sexual function may be harmed after treatment for rectal cancer. This study aimed to evaluate prospectively the incidence of sexual dysfunction after rectal cancer treatment and to compare the effects of laparoscopic and traditional open approaches in terms of postoperative sexual function. METHODS: Baseline and 3-, 6-, and 12-month assessments of sexual dysfunction using the International Index of Erectile Function (IIEF) and its specific domains prospectively took place for 56 patients who underwent rectal cancer surgery (38 open vs. 18 laparoscopic procedures, 38 low anterior vs. 18 abdominoperineal resections). The preliminary results are presented. RESULTS: The average total IIEF and isolated IIEF response domain scores were significantly decreased after surgery (p < 0.01) except for the intercourse satisfaction and overall satisfaction scores at 12 months. An improvement in IIEF scores was observed between the 3- and 6-month assessment points (p < 0.01) except for the erectile function and orgasmic function scores. No significant differences were observed between the open and laparoscopic groups in the total IIEF and domain scores preoperatively and at the 3- and 6-month assessment points. The rates of sexual dysfunction did not differ significantly preoperatively or at 3 months postoperatively when open and laparoscopic procedures were compared, although there was a trend in favor of laparoscopic surgery at 6 months (p = 0.076). The baseline IIEF score and the baseline, 3-, and 6-month sexual desire scores were better (p = 0.035, 0.004, 0.017, and 0.061, respectively) in the low anterior resection group than in the abdominoperineal resection group. CONCLUSIONS: Rectal cancer resections were postoperatively associated with a significant reduction in IIEF scores and high rates of sexual dysfunction at 3 and 6 months. The IIEF and domain scores at different assessment points were comparable between the laparoscopic and open surgery groups. Extending the monitoring period and adding more patients in this ongoing prospective study will further elucidate postoperative sexual dysfunction after rectal cancer surgery.

P53 and EGFR expression in colorectal cancer: a reappraisal of 'old' tissue markers in patients with long follow-up.

BACKGROUND: Extensive research into the biology of colorectal cancer has identified a plethora of molecular markers reputed to provide prognostic information. During the last two decades conflicting results have been drawn on the role of the p53 tumour suppressor gene and of the first identified member of the type receptor tyrosine kinase family, EGFR, on colorectal cancer prognosis, p53 Mutational status has been associated with both improved and reduced survival. EGFR has been associated with reduced length of survival, increasing Dukes' stage and lymph node metastases in several reports, but as many studies have reported no association with unfavourable prognostic parameters. The aim of this study was to evaluate the p53 and EGFR expression in patients with an at least 5-year follow-up. PATIENTS AND METHODS: Paraffin-embedded material was retrospectively collected from 164 colorectal adenocarcinoma (50 rectal) patients, who had been operated on between 1994 and 2003. The median follow-up was 5 years (range: 1-14). p53 and EGFR expression were evaluated by immunohistochemistry. RESULTS: Positive p53 immunostaining and EGFR expression was observed in 63.4% and 43.9% of patients, respectively. p53 and EGFR positivity rates were significantly interrelated (p = 0.004). No significant correlation was found with the examined clinicopathological parameters except for advanced T-stage, which demonstrated significant associations with p53 expression (p = 0.004), EGFR expression (p = 0.0001) and p53/EGFR coexpression (p = 0.001). In univariate survival analysis (log rank test), stage (p = 0.0001), lymphovascular invasion (p = 0.005) and perineural infiltration (p = 0.004) were associated with the overall cancer-specific survival, while a trend existed for EGFR (p = 0.06) and p53/EGFR coexpression (p = 0.07). On multivariate analysis, only stage was associated with increased risk of cancer death (Cox regression analysis p = 0.0001, b-coefficient (SE): 1.898 (0.383). CONCLUSION: p53 and EGFR were overexpressed in this colorectal cancer patient population and were significantly associated with advanced T stage. In the context of new therapeutic strategies using EGFR-targeted therapies, although EGFR remains a controversial prognostic factor, this expression-stage association may play a crucial role in a decision to initiate an adjuvant treatment.