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techniques combined were scored for the likelihood of tumour in each area and results were compared with whole-mount analysis.• The area under the receiver operating characteristic curve ( A z ) was used to evaluate accuracy for tumour detection. The association between MR accuracy and Gleason score was statistically assessed. RESULTS• Of the 456 prostate octants analysed, 145 showed cancer on whole-mount analysis, 120 (83%) of them with a diameter assumed to correspond to a volume > 0.2 cm 3 . Gleason score was ≥ 7 in 68 (47%) tumours.• In the PZ, the A z value was significantly higher for T2W + DWI, T2W + DCE and all three techniques combined than for T2W alone ( P < 0.05).• In the TZ, the A z value was higher for T2W + DWI than for T2W alone, but the difference was not significant.• The A z value for T2W + DWI was significantly higher than that for T2W + DCE or for the three sequences combined.• Gleason score was significantly associated with cancer detection in the PZ. CONCLUSIONS• Adding DWI and DCE to T2W imaging increased MRI performance in cancer detection in the PZ significantly.• However, this multiparametric model failed to improve performance in the TZ.• Gleason score significantly influenced cancer detection in the PZ but not in the TZ.

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The cyclic GMP-AMP synthase/stimulator of IFN genes (cGAS/STING) pathway detects cytosolic DNA to activate innate immune responses. Poly(ADP-ribose) polymerase inhibitors (PARPi) selectively target cancer cells with DNA repair deficiencies such as those caused by BRCA1 mutations or ERCC1 defects. Using isogenic cell lines and patient-derived samples, we showed that ERCC1-defective non-small cell lung cancer (NSCLC) cells exhibit an enhanced type I IFN transcriptomic signature and that low ERCC1 expression correlates with increased lymphocytic infiltration. We demonstrated that clinical PARPi, including olaparib and rucaparib, have cell-autonomous immunomodulatory properties in ERCC1-defective NSCLC and BRCA1-defective triple-negative breast cancer (TNBC) cells. Mechanistically, PARPi generated cytoplasmic chromatin fragments with characteristics of micronuclei; these were found to activate cGAS/STING, downstream type I IFN signaling, and CCL5 secretion. Importantly, these effects were suppressed in PARP1-null TNBC cells, suggesting that this phenotype resulted from an on-target effect of PARPi on PARP1. PARPi also potentiated IFN-γ-induced PD-L1 expression in NSCLC cell lines and in fresh patient tumor cells; this effect was enhanced in ERCC1-deficient contexts. Our data provide a preclinical rationale for using PARPi as immunomodulatory agents in appropriately molecularly selected populations.

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Urothelial bladder cancer (UBC) is rare in young patients and as a result little information as to tumor type and clinical course are available. We present clinicopathological data of a large series of patients less than 40 years with bladder carcinoma. We included in this retrospective study covering the period from 1992 to 2013 patients less than 40 years with a first diagnosis of bladder cancer. Lesions were classified according to the WHO 2004 classification by uropathologists of ten centers. Stage, grade, multifocality, smoking habits, recurrence, and survival were studied. The cohort comprised of 152 patients, 113 males and 39 females with a mean age of 33.2 years. The large majority of the patients (142) was diagnosed with an urothelial carcinoma, the ten others with various histopathological diagnoses. In the age group less than 30 years old, 40.3 % of the cases concerned a papillary urothelial neoplasia of low malignant potential (PUNLMP). In the age group over 30 years, the proportion of PUNLMP decreased to 27.2 %. Only 5.6 % of the UBC was associated with carcinoma in situ. In 14.1 %, a high grade muscle invasive UC was found; 7.0 % had lymph node and 4.9 % distant metastasis at time of presentation. Four patients presented with a history of schistosomiasis; all had an infiltrating carcinoma. After initial resection, 36 patients relapsed, 17 % as PUNLMP, 53 % as pTa low grade, and 30 % as pTa-pT2 high grade UC. During follow-up, 6 % of the patients died. PUNLMP is the most frequent entity in this patient group. It is important that the PUNLMP entity is maintained in future classification systems.

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