Sensitization of osteosarcoma to irradiation by targeting nuclear FGFR1.

Over the past 25 years, chemotherapy regimens for osteosarcoma have failed to improve the 65-70% long-term survival rate. Radiation therapy is generally ineffective except for palliative care. We here investigated whether osteosarcoma can be sensitized to radiation therapy targeting specific molecules in osteosarcoma. Large-scale RNA sequencing analysis in osteosarcoma tissues and cell lines revealed that FGFR1 is the most frequently expressed receptor tyrosine kinase in osteosarcoma. Nuclear FGFR1 (nFGFR1) was observed by subcellular localization assays. The functional studies using a FGFR1IIIb antibody or small molecule FGFR1 inhibitors showed that nFGFR1, but not membrane-bound FGFR1, induces G2 cell-cycle checkpoint adaptation, cell survival and polyploidy following irradiation in osteosarcoma cells. Further, the activation of nFGFR1 induces Histone H3 phosphorylation at Ser 10 and c-jun/c-fos expression to contribute cell survival rendering radiation resistance. Furthermore, an in vivo mouse study revealed that radiation resistance can be reversed by the inhibition of nFGFR1. Our findings provide insights into the potential role of nFGFR1 to radiation resistance. Thus, we propose nFGFR1 could be a potential therapeutic target or a biomarker to determine which patients might benefit from radiation therapy.

Unusual appearance of an adrenal ganglioneuroma.

Ganglioneuromas are rare tumors that occur spontaneously or arise from a poorly differentiated neuroblastic tumor. Although they are typically described in the pediatric population, they can occur in adults. Ganglioneuromas are often discovered incidentally and their typical imaging appearance, although non-specific, is that of a well-defined solid mass. We are presenting a case of a fat-containing adrenal lesion in a 53-year-old male. The extensive lipomatous changes within the lesion led to the presumption that it represented an adrenal myelolipoma. Pathology revealed a ganglioneuroma with extensive lipomatous changes. This is an uncommon presentation of an adrenal ganglioneuroma mimicking an adrenal myelolipoma. The diagnosis of an adrenal ganglioneuroma raises the possibility of syndromic associations for which patients may undergo genetic testing. We provide a review of typical imaging features of an adrenal ganglioneuroma and provide insight into the situations in which a ganglioneuroma can be suggested as a diagnostic consideration.

Gleason grading challenges in the diagnosis of prostate adenocarcinoma: experience of a single institution.

Gleason score (GS) is an important factor in determining management and outcome of prostate adenocarcinoma. A standard GS scheme was introduced by ISUP 2005 consensus conference, but there is still significant discordance in grading prostate adenocarcinomas among pathologists, especially between genitourinary-trained (GU) and non-GU pathologists. All biopsies from outside institutions referred for definitive treatment in our hospital are reviewed by a GU pathologist for confirmation and quality assurance. From 2011 to 2013, 117 consecutive prostate consults were retrieved and compared with the initial outside reports as well as final radical prostatectomy (RP) results. Follow-up prostate specific antigen (PSA) was assessed pre- and post-RP, and the results were analyzed. The overall initial GS was higher for all specimens (p = 0.007) especially for the RP cases (p = 0.002). Overall, the modal GS on initial diagnosis was GS7(4 + 3) that was downgraded to the modal GS6(3 + 3) upon review. Despite an overall substantial agreement between the non-GU and GU pathologists [ICC = 0.66], GS by GU pathologist had higher correlation with the final GS in the RP specimen [ICC = 0.62] than non-GU pathologist [ICC = 0.48]. GS on all reviewed cases were found to correlate significantly with the pre-operative PSA (p = 0.002) but the same was not true for the initial report. A non-GU pathologist is more likely to assign a higher GS than a GU pathologist, with a trend to overcall Gleason pattern 4. Considering the implications on treatment, close attention must be paid to the ISUP 2005 consensus conference recommendations.