Histopathology of prostate tissue after vascular-targeted photodynamic therapy for localized prostate cancer

Low-risk prostate adenocarcinoma is classically managed either with active surveillance or radical therapy (such as external radiotherapy or radical prostatectomy), but both have significant side effects. Vascular-targeted photodynamic therapy (VTP) is a focal therapy proposed as an alternative approach for localized, low-volume, and low-Gleason score (≤6) carcinomas. We report histological modifications observed in prostate biopsies of 56 patients, performed 6 months after VTP using the photosensitizer TOOKAD® Soluble (WST11) and low-energy laser administered in the tumor area transperineally by optic fibers. In 53 patients, we observed sharply demarcated hyaline fibrotic scars, with or without rare atrophic glands, sometimes reduced to corpora amylacea surrounded by giant multinuclear macrophages. Mild chronic inflammation, hemosiderin, and coagulative necrosis were also observed. When residual cancer was present in a treated lobe (17 patients), it was always located outside the scar, most often close to the prostate capsule, and it showed no therapy-related modification. Histopathological interpretation of post-WST11 VTP prostate biopsies was straightforward, in contrast with that of prostate biopsies after radio or hormonal therapy, which introduces lesions difficult to interpret. VTP resulted in complete ablation of cancer in the targeted area

Relationship Between the Expression of O-Methylguanine-DNA Methyltransferase (MGMT) and p53, and the Clinical Response in Metastatic Pancreatic Adenocarcinoma Treated with FOLFIRINOX

BACKGROUND: To date, no predictive biomarker for the efficacy of FOLFIRINOX in metastatic pancreatic adenocarcinoma has been demonstrated. Deficiency in O-methylguanine-DNA methyltransferase (MGMT) has been associated with a therapeutic response in endocrine tumors of the pancreas and the lack of expression of protein 53 (p53) could interfere with the action of MGMT. OBJECTIVE: The aim of our study was to assess the prevalence of MGMT and p53 in patients with metastatic pancreatic adenocarcinoma treated with FOLFIRINOX as a first-line treatment and to investigate their association with therapeutic response and survival. PATIENTS AND METHODS: The immunohistochemical expression of MGMT was recorded as present or absent and the expression of p53 was semi-quantitatively scored in 30 patients with metastatic pancreatic adenocarcinoma, at Angers Hospital in France between September 2011 and June 2015. Clinical and radiologic data were collected retrospectively. RESULTS: The presence or absence of MGMT expression entailed no significant differences in response rate. Median values of progression-free survival (PFS) and overall survival (OS) were lower in patients with MGMT expression, but sample size is too small to conclude that there is a statistically significant difference. No significant relationship for response rate and PFS was observed in relation with p53 expression. By contrast, patients with a strong tumor expression of p53 had a significantly lower OS compared to patients with no or weak expression of the protein (p = 0.027). There was a positive correlation between the expression of p53 and MGMT (p = 0.08). CONCLUSIONS: These preliminary findings suggest that for patients treated with FOLFIRINOX as a first-line treatment for metastatic pancreatic adenocarcinoma, the immunohistochemical evaluation of MGMT could not predict the clinical outcome; however, the survival was not significant probably because of the under-powered study (due to small sample size). A strong tumor expression of p53 is associated with a poor prognosis of OS

Nicotinamide N-méthyltransférase (NNMT) : biomarqueur potentiel de l’agressivité du carcinome rénal à cellules claires

Objectifs NNMT (nicotinamide N-méthyltransférase) est une enzyme de la voie des pyridines. Les études d’analyse protéomique ont démontré sa surexpression dans le carcinome rénal à cellules claires (CRCC). Des études de validation immunohistochimiques ont montré son association avec les tumeurs à risque d’évolution défavorable. Nous avons voulu étudier le lien entre la survie de patients atteints de CRCC et l’expression tissulaire de NNMT comme potentiel biomarqueur. Méthodes Nous avons inclus de manière prospective au sein de la base de données nationale UroCCR 137 patients opérés d’un CRCC. Nous avons étudié l’intensité du marquage cellulaire intracytoplasmique de NNMT (cotée de 0 à 3) évaluée par le même pathologiste pour l’ensemble des tumeurs et nous avons étudié la corrélation entre cette donnée de pathologie cellulaire et la survie (globale et sans récidive) des patients en fonction de l’âge et de l’agressivité tumorale définie grâce au score SSIGN (pTNM, taille tumorale, grade histopronostique de Fuhrman et présence de nécrose). Le test du log rank et le modèle de Cox étaient utilisés. Résultats Nous avons inclus dans notre étude 126 patients (onze patients avec des données manquantes). L’intensité du marquage tissulaire intracytoplasmique de NNMT était cotée à 0 (absente) dans 7 cas, à 1 (faible) dans 20 cas, à 1,5 dans 28 cas, à 2 (intermédiaire) dans 27 cas, à 2,5 dans 19 cas et à 3 (élevée) dans 25 cas. Un score SSIGN ≤ 6 était retrouvé dans 89 cas et un score SSIGN > 6 dans 38 cas. Durant la première année de suivi, une intensité cellulaire de NNMT > 2,5 était associée à un pronostic défavorable indépendamment du score SSIGN (p = 10–3). Ce seuil d’intensité cellulaire était associé à des tumeurs de score SSIGN > 6 (p = 0,01) de moins bon pronostic. Conclusion Nous avons démontré qu’une intensité intracytoplasmique élevée de NNMT, évaluée en anatomocytopathologie, était associée à une évolution péjorative des patients atteints d’un CRCC durant la première année de suivi indépendamment de l’agressivité de leur tumeur. Il s’agit d’un biomarqueur corrélé à des tumeurs agressives de score SSIGN > 6 ce qui souligne le rôle potentiel de NNMT comme biomarqueur histopronostique du CRCC. NNMT pourrait présenter un intérêt dans la sélection des patients nécessitant un traitement adjuvant

Functional characterization of the 12p12.1 renal cancer-susceptibility locus implicates BHLHE41

Genome-wide association studies have identified multiple renal cell carcinoma (RCC) susceptibility loci. Here, we use regional imputation and bioinformatics analysis of the 12p12.1 locus to identify the single-nucleotide polymorphism (SNP) rs7132434 as a potential functional variant. Luciferase assays demonstrate allele-specific regulatory activity and, together with data from electromobility shift assays, suggest allele-specific differences at rs7132434 for AP-1 transcription factor binding. In an analysis of The Cancer Genome Atlas data, SNPs highly correlated with rs7132434 show allele-specific differences in BHLHE41 expression (trend P value=6.3 × 10(-7)). Cells overexpressing BHLHE41 produce larger mouse xenograft tumours, while RNA-seq analysis reveals that constitutively increased BHLHE41 induces expression of IL-11. We conclude that the RCC risk allele at 12p12.1 maps to rs7132434, a functional variant in an enhancer that upregulates BHLHE41 expression which, in turn, induces IL-11, a member of the IL-6 cytokine famil

Borderline ovarian tumors: Guidelines from the French national college of obstetricians and gynecologists (CNGOF)

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Borderline ovarian tumors: French guidelines from the CNGOF. Part 2. Surgical management, follow-up, hormone replacement therapy, fertility management and preservation

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Borderline ovarian tumors: French guidelines from the CNGOF. Part 1. Epidemiology, biopathology, imaging and biomarkers

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