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1.  Bladder cancer in HIV-infected adults: an emerging concern? 
Journal of the International AIDS Society  2014;17(4Suppl 3):19647.
Introduction
As HIV-infected patients get older more non-AIDS-related malignancies are to be seen. Cancer now represents almost one third of all causes of deaths among HIV-infected patients [1]. Albeit bladder cancer is one of the most common malignancy worldwide [2], only 13 cases of bladder cancer in HIV-infected patients have been reported in the literature so far [3].
Materials and Methods
We conducted a monocentric study in our hospital. We selected all patients who were previously admitted (from 1998 to 2013) in our hospital with diagnoses of HIV and bladder cancer. The objective was to assess the prevalence and characteristics of bladder cancers in HIV-infected patients in our hospital.
Results
Based on our administrative HIV database (6353 patients), we found 15 patients (0.2%) with a bladder cancer. Patients’ characteristics are presented in Table 1. Patients were mostly men and heavy smokers. Their median nadir CD4 cell count was below 200 and most had a diagnosis of AIDS. A median time of 14 years was observed in those patients, between the diagnosis of HIV-infection and the occurrence of bladder cancer, although in patients much younger (median age 56) than those developing bladder cancer without HIV infection (71.1 years) [4]. Haematuria was the most frequent diagnosis circumstance in HIV-infected patients who had relatively preserved immune function on highly active antiretroviral therapy (HAART). Histopathology showed relatively advanced cancers at diagnosis with a high percentage of non transitional cell carcinoma (TCC) tumor and of TCC with squamous differentiation, suggesting a potential role for human papilloma virus (HPV) co-infection. Death rate was high in this population.
Conclusions
Bladder cancers in HIV-infected patients remain rare but occur in relatively young HIV-infected patients with a low CD4 nadir, presenting with haematuria, most of them being smokers, and have aggressive pathological features that are associated with severe outcomes.
doi:10.7448/IAS.17.4.19647
PMCID: PMC4224926  PMID: 25394151
2.  A Meta-Analysis of the Relationship between FGFR3 and TP53 Mutations in Bladder Cancer 
PLoS ONE  2012;7(12):e48993.
TP53 and FGFR3 mutations are the most common mutations in bladder cancers. FGFR3 mutations are most frequent in low-grade low-stage tumours, whereas TP53 mutations are most frequent in high-grade high-stage tumours. Several studies have reported FGFR3 and TP53 mutations to be mutually exclusive events, whereas others have reported them to be independent. We carried out a meta-analysis of published findings for FGFR3 and TP53 mutations in bladder cancer (535 tumours, 6 publications) and additional unpublished data for 382 tumours. TP53 and FGFR3 mutations were not independent events for all tumours considered together (OR = 0.25 [0.18–0.37], p = 0.0001) or for pT1 tumours alone (OR = 0.47 [0.28–0.79], p = 0.0009). However, if the analysis was restricted to pTa tumours or to muscle-invasive tumours alone, FGFR3 and TP53 mutations were independent events (OR = 0.56 [0.23–1.36] (p = 0.12) and OR = 0.99 [0.37–2.7] (p = 0.35), respectively). After stratification of the tumours by stage and grade, no dependence was detected in the five tumour groups considered (pTaG1 and pTaG2 together, pTaG3, pT1G2, pT1G3, pT2-4). These differences in findings can be attributed to the putative existence of two different pathways of tumour progression in bladder cancer: the CIS pathway, in which FGFR3 mutations are rare, and the Ta pathway, in which FGFR3 mutations are frequent. TP53 mutations occur at the earliest stage of the CIS pathway, whereas they occur would much later in the Ta pathway, at the T1G3 or muscle-invasive stage.
doi:10.1371/journal.pone.0048993
PMCID: PMC3521761  PMID: 23272046
3.  Prevalence and spectrum of microsatellite alterations in nonmuscle invasive bladder cancers 
We aimed to identify interesting deleted chromosomal regions for bladder cancer diagnosis and carcinogenesis, and to evaluate the association between loss of heterozygosity (LOH) and clinico-pathological parameters. Microsatellite analysis was performed on urine sediment and tumor tissue from 43 consecutive patients with superficial transitional cell carcinoma (TCC) and from 42 consecutive controls. Informative cases were scored as LOH or allelic loss (AL) according to the decrease of the allelic-imbalance ratio. The prevalence of LOH and AL was 39.5% and 86%, respectively. Chromosome 9 was the most frequently altered, especially at 9p (35%). The total number of microsatellite alterations per analysis was correlated with age, grade, stade and EAU classification. The locus 17p13.1 was strongly associated with high-stage (p=0.01) and high-grade tumors (p=0.02). Specificity and sensitivity of LOH was 100% and 39.3% for diagnosis of malignant urinary disease. Specificity and sensitivity of AL was 73.8% and 88%, respectively. Allelic losses are a frequent and early event in bladder cancer, especially at 9p. Thanks to its high specificity, LOH may serve as a complementary tool for non invasive diagnosis of bladder cancer. Further study is warranted to evaluate the prognostic value of LOH on recurrence, progression and muscle invasion.
PMCID: PMC3189821  PMID: 21994900
Bladder cancer; microsatellite; loss of heterozygosity; allelic loss
4.  The prognostic value of FGFR3 mutational status for disease recurrence and progression depends on allelic losses at 9p22 
Developing molecular markers that define high-risk lesions is clinically critical for improving the prognosis determination of the tumors and their treatment. We decided to focus on the two pathways involving FGFR3 and allelic losses at 9p22 to identify a potential combined role in predicting tumor recurrence, progression and/or muscle. Microsatellite and mutational FGFR3 status analyses was performed in tumor tissue of 58 patients in a prospective unicentre study. The results of microsatellite and FGFR3 analyses were dichotomized as follows: loss of heterozygos-ity (LOH) versus retention of heterozygosity (ROH) on the one hand; mutant FGFR3 (mtFGFR3) versus wild-type FGFR3 (wtFGFR3) on the other hand. The combined 9p22/FGFR3 status was strongly correlated with stage (p=0.001) and grade (p<0.001) whereas the single FGFR3 mutational status was not able to predict recurrence, progression or muscle invasion. The survival curves corresponding to each combined status (mtFGFR3/ROH, wtFGFR3/ROH, mtFGFR3/LOH, wtFGFR3/LOH) were significantly different for recurrence (p=0.008), progression (p=0.046) and progression to muscle invasive disease (p=0.004). In case of 9p22 LOH, the FGFR3 mutational status was strongly associated with different clinical outcomes. In a multivariate model, the combined wtFGFR3/9p22 LOH status remained significant in predicting oncologic outcomes. FGFR3 mutations strongly characterize tumors with low malignant potential and favourable clinical outcome in case of allelic losses at 9p22, whereas its prognostic value becomes null or slightly inverts in case of allelic stability. Thus, our findings may also lead to further experiments in order to study interactions between FGFR3 and genes located at 9p22, as CDKN2A.
PMCID: PMC3186048  PMID: 21984968
Bladder cancer; FGFR3; loss of heterozygosity; prognosis; mutations
5.  Determination of Angptl4 mRNA as a Diagnostic Marker of Primary and Metastatic Clear Cell Renal-Cell Carcinoma 
PLoS ONE  2010;5(4):e10421.
Background
We have previously shown that angiopoietin-like 4 (angptl4) mRNA, a hypoxia-inducible gene, is highly expressed in clear cell renal-cell carcinoma (ccRCC), the most common subtype of RCC for which no specific marker is available. We here investigated whether angptl4 mRNA 1) could be a useful diagnostic and/or prognostic marker of ccRCC in a large and comprehensive retrospective series, 2) induction is dependent on the VHL status of tumors.
Methodology/Principal Findings
Using in situ hybridization, we report that angptl4 mRNA is expressed in 100% of both sporadic (n = 102) and inherited (n = 6) primary ccRCCs, without any statistical association with nuclear grade (p = 0.39), tumor size (p = 0.09), stage grouping (p = 0.17), progression-free survival (p = 0.94), and overall survival (p = 0.80). Angptl4 mRNA was also expressed in 26 (87%) of 30 secondary ccRCCs but neither in any other secondary RCCs (n = 7). In contrast, angptl4 mRNA was neither expressed in 94% non-ccRCC renal tumors (papillary RCCs (n = 46), chromophobe RCCs (n = 28), and oncocytomas (n = 9)), nor in non-renal clear cell carcinomas (n = 39). Angptl4 expression was also examined in tumors associated (n = 23) or not associated (n = 66) with VHL disease. 40 (98%) hemangioblastomas expressed angptl4 whereas all pheochromocytomas (n = 23) and pancreatic tumors (n = 25) were angptl4-negative, whatever their VHL status.
Conclusions/Significance
Angptl4 mRNA expression was highly associated with ccRCC (p = 1.5 10−49, Chi square test) allowing to define its expression as a diagnosis marker for primary ccRCC. Moreover, angptl4 mRNA allows to discriminate the renal origin of metastases of clear-cell carcinomas arising from various organs. Finally, inactivation of VHL gene is neither necessary nor sufficient for angptl4 mRNA induction.
doi:10.1371/journal.pone.0010421
PMCID: PMC2861680  PMID: 20454689
6.  Salvage radiotherapy for patients with PSA relapse after radical prostatectomy: a single institution experience 
BMC Cancer  2008;8:26.
Background
To assess the efficacy of salvage radiotherapy (RT) for persistent or rising PSA after radical prostatectomy and to determine prognostic factors identifying patients who may benefit from salvage RT.
Methods
Between 1990 and 2003, 59 patients underwent RT for PSA recurrence after radical prostatectomy. Patients received a median of 66 Gy to the prostate bed with 3D or 2D RT. The main end point was biochemical failure after salvage RT, defined as an increase of the serum PSA value >0.2 ng/ml confirmed by a second elevation.
Results
Median follow-up was 38 months. The 3-year and 5-year bDFS rates were 56.1% and 41.2% respectively. According to multivariate analysis, only preRT PSA ≥1 ng/ml was associated with biochemical relapse.
Conclusion
When delivered early, RT is an effective treatment after radical prostatectomy. Only preRT PSA ≥1 ng/ml predicted relapse.
doi:10.1186/1471-2407-8-26
PMCID: PMC2257956  PMID: 18230130

Results 1-6 (6)