Jorge Leon

Prognostic Significance of p53 Mutation and p53 Overexpression in Advanced Epithelial Ovarian Cancer: A Gynecologic Oncology Group Study

PURPOSE The prognostic significance of p53 mutations and overexpression in advanced epithelial ovarian cancers was examined in primary tumors from 125 patients participating in a Gynecologic Oncology Group randomized phase III treatment protocol. PATIENTS AND METHODS Mutational analysis of p53 was performed in RNA or genomic DNA extracted from frozen tumor. An immunohistochemistry assay was used to detect p53 overexpression in fixed tumor. RESULTS There were 81 patients (74%) with a single mutation, three patients (3%) with two mutations, and 25 patients (23%) lacking a mutation in exons 2 to 11 of p53. Although most mutations occurred within exons 5 to 8, mutations outside this region were observed in 11% of patients. A mutation in exons 2 to 11 of p53 was associated with a short-term improvement in overall survival and progression-free survival. Adjusted Cox modeling demonstrated a 70% reduction in risk of death (P =.014) and a 60% reduction in risk of disease progression (P =.014) for women with such mutations. However, these striking risk reductions increased over time (P <.02) and eventually disappeared with longer follow-up. Overexpression of p53 was observed in 55 patients (100%) with only missense mutation(s), seven patients (32%) with truncation mutations, and eight patients (40%) lacking a mutation in exons 2 to 11. Overexpression of p53 was associated with tumor grade but not with patient outcome. CONCLUSION Alterations in p53 are a common event in advanced epithelial ovarian cancer. A mutation in p53, but not overexpression of p53, is associated with a short-term survival benefit. Additional studies are required to define the roles that p53 plays in regulating therapeutic responsiveness and patient outcome.

Distribution of Neural Tube Defects as a Function of Maternal Weight:No Apparent Correlation

Objectives: Maternal nutritional deficiency is an important predisposing factor to congenital neural tube defects (NTDs). It was hypothesized that obese women may have an increased risk for NTDs. The aim of the present study was to address this question in a large cohort. Methods: A total of 72,915 consecutive cases of biochemical screening that had documented maternal weights and pregnancy outcomes were identified from the Quest Diagnostic Laboratories database. Patients were divided into five ranges of maternal weights, and the incidence of NTDs was calculated for each group. Based on the different definitions of maternal overweight, the data were also analyzed based on 2 groups only, obese and nonobese, using three cutoff points. Results: Seventy-nine pregnancies were complicated by NTDs (incidence of 1.08 per 1,000 pregnancies). Differences between maternal weights ranges were not found to be statistically significant (χ2 = 5.997, p = 0.19, power = 0.99). Differences between obese and nonobese mothers were not found to be statistically significant for all three analyses as well. Conclusions: Our present results do not support an association between maternal obesity and NTDs.

Combination of elevated maternal serum alpha-fetoprotein (MSAFP) and low estriol is highly predictive of anencephaly

Increased levels of second trimester maternal serum alpha-fetoprotein (MSAFP) have long been established as a marker for neural tube defects (NTDs). In addition, decreased levels of maternal estriol in the third trimester have been reported in pregnancies with anencephalic fetuses. The purpose of this study was to evaluate whether early second trimester unconjugated serum estriol (uE3) is an independent predictor of NTDs. The study included 57,031 patients who underwent maternal serum screening with MSAFP at 14-22 weeks gestation. Of these, 23,415 also had uE3 measurements. There were 63 cases of NTD, an overall incidence of 1.1 per 1,000. Elevated MSAFP (> or =2.5 MOM) was detected in 1,346 patients, 48 of which had NTDs. Decreased uE3 (< or =0.5) was detected in 1,437 patients, 17 of which had NTDs. The incidence of NTDs was significantly higher in patients with low uE3, compared to patients with normal/high uE3 (1.15% vs. 0.09%, P < 001). Finally, 51 patients had both increased MSAFP and decreased uE3; 16 of these had NTDs, 14 of which were anencephalics. In conclusion, both elevated MSAFP and low maternal serum estriol are predictive of NTD but have a low sensitivity. The combination of abnormally elevated MSAFP and low estriol is highly predictive of NTD in particular anencephaly.

Urinary β-Core Fragment as a Predictor of Abnormal Pregnancy at 4–6 Weeks’ Gestation

Currently, transvaginal ultrasound and serial serum beta-hCG measurements are used to differentiate normal versus abnormal gestations in the first trimester of pregnancy. These techniques have been found to be ineffective when the gestations are earlier than 6 weeks. This study was conducted to determine if urinary beta-core fragment, the urine degradation product of beta-hCG, could be used to distinguish normal from abnormal gestations between 4 and 6 weeks. Urine samples were obtained from 27 patients on initial presentation to the emergency room or outpatient settings with gestations at 4-6 weeks by sure last menstrual period. The urine was then frozen at -40 degrees C and sent for beta-core assay analysis. Eighteen women with normal intrauterine pregnancies and nine abnormal pregnancies, including ectopics and spontaneous abortions, were studied. Pearson correlations were performed with a p < 0.05 considered significant. In the normal gestations, there was a positive correlation between beta-core fragment and gestational age at 4-6 weeks (r = 0.461, p < 0.05). This correlation was not evident in abnormal gestations (r = 0.360, p = 0.34). In early pregnancy, beta-core fragment correlates positively with gestational age which is not apparent in abnormal counterparts. This finding suggests that urinary beta-core fragment may be a promising marker to differentiate normal early pregnancies from abnormal gestations.

Impact of modified Glasgow prognostic score and neutrophil/platelet-lymphocyte ratio on survival metastatic colorectal cancer (mCRC).

e15557Background: Modified Glasgow Prognostic Score (mGPS), was reported as a good prognostic factor for OS, in other neoplasms, however its role in mCRC it’s still being studied. High circulating ...

Prognostic value of neutrophil- (NLR) and platelet-lymphocyte ratio (PLR) in patients with metastatic colorectal cancer (mCRC) with KRAS, BRAF: A Peruvian point of view.

e15550Background: High circulating neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) appears to be prognostic in metastatic colorectal cancer (mCRC), they have been suggested as...