Rahmene Azzouzi

Prostate carcinoma risk and allelic variants of genes involved in androgen biosynthesis and metabolism pathways

Ethnicity, when it is used to mean shared genetic inheritance within a group, has become one of the most important factors in determining prostate carcinoma risk. Genetic polymorphisms were hypothesized to be the probable explanation for differences in risk among ethnic groups. The authors evaluated the association between polymorphisms in genes involved in the androgen biosynthesis and metabolism pathway and the risk of prostate carcinoma.

Early-onset hereditary prostate cancer is not associated with specific clinical and biological features.

Familial prostate cancer (CaP) accounts for 15–20% of all CaP, and hereditary CaP for 5–10% of patients. Few data are available concerning their clinical and biological features.

Segregation Analysis of Prostate Cancer in France: Evidence for Autosomal Dominant Inheritance and Residual Brother-brother Dependence

Four segregation analyses concerning prostate cancer (CaP), three conducted in the United States and one in Northern Europe, have shown evidence for a dominant major gene but with different parameter estimates. A recent segregation analysis of Australian pedigrees has found a better fit of a two‐locus model than single‐locus models. This model included a dominantly inherited increased risk that was greater at younger ages and a recessively inherited or X‐linked increased risk that was greater at older ages. Recent linkage analyses have led to the detection of at least 8 CaP predisposing genes, suggesting a complex inheritance and genetic heterogeneity.

PGE2 and LTB4 tissue levels in benign and cancerous prostates.

PGE2 and LTB4 are involved in inflammation and carcinogenesis in several tissues but have not been studied in prostate cancer and hyperplasia until now. We therefore measured PGE2 and LTB4 productions in a total of 206 prostate tissues from 116 patients including benign hyperplastic (90), pericancerous (106) and cancerous samples (10). We also analysed the influence of inflammation levels, prostate volume and glandular to epithelial ratio. PGE2 and LTB4 concentrations were measured using specific enzyme immunoassay kits. There was a correlation between PGE2 level, prostatic volume, inflammation score, and decreased glandular surface. By contrast, there was no correlation between LTB4 levels and inflammation or PGE2 production. Cancerous samples had higher LTB4 levels than pericancerous samples, but there was no difference in PGE2 levels. PGE2 and inflammation may be associated to stromal benign prostatic hyperplasia whereas LTB4 may play a role in prostate carcinogenesis.

1775 COMPARISON OF TWO MAJOR PROGNOSTIC MODELS FOR PATIENTS WITH METASTATIC RENAL CELL CARCINOMA TREATED IN THE CONTEMPORARY ERA OF TARGETED THERAPIES

4660 Background: The 2 most popular prognostic systems for patients with metastatic renal cell carcinoma (mRCC) are MSKCC and French Group of Immunotherapy (FGI) models. Both systems have initially been established by using cohorts of patients treated with cytokines. No direct comparison of these 2 models has been published so far in the modern era of targeted therapies. Our goal was to compare their effectiveness in predicting overall survival (OS) in mRCC patients treated with anti-angiogenic drugs. METHODS Based on an international cohort of 965 mRCC patients from 18 tertiary care centers treated with systemic treatment, we assessed OS in univariate Cox regression according to both prognostic models stratification. Then, variables of each model were compared in multivariate Cox regression. Area under the curve (AUC) of both model was also calculated. RESULTS Median OS for the entire population was 31.8 months. Both systems were able to distinguish 3 groups with statistically significantly different survivals. Median OS in good, intermediate and poor prognostic group were 45.9, 23.5, 13.5 months and 50.9, 33.4, 13.5 months in MSKCC and FGI models, respectively. In multivariate Cox regression analysis, 3 out of the 5 variables of MSKCC model achieved independent prognostic value (haemoglobin level (HR=1.79, p=0.001), LDH elevation (HR=4.3; p=0.001) and Performance Status (HR=1.71; p=0.006). Similarly, 3 out of the 5 variables of the FGI model achieved independent prognostic status (haemoglobin level (HR=1.74; p=0.04); number of metastasis (HR=2.2; p=0.008) and performance status (HR=2.12; p=0.006). AUC of MSKCC and FGI models were 0.57 and 0.65, respectively. When focusing on 369 patients who received sunitinib as first line treatment, AUC of MSKCC and FGI models were 0.66 and 0.75, respectively. CONCLUSIONS MSKCC and FGI are both effective prognostic models in predicting OS in mRCC patients treated in the contemporary period. However, based on our data, FGI model seems to exhibit a better predictive accuracy than MSKCC model. The prognostic role of FGI model should be therefore revisited in the era of targeted therapies.