3 research outputs found
Gene Fusion Characterization of Rare Aggressive Prostate Cancer Variants ‐ Adenosquamous Carcinoma, Pleomorphic Giant Cell Carcinoma, and Sarcomatoid Carcinoma: An Analysis of 19 Cases
Aims
We evaluated the molecular underpinnings of rare aggressive prostate cancer variants adenosquamous, pleomorphic giant cell, and sarcomatoid carcinomas.
Methods and Results
We retrieved 19 tumors with one or more variant(s) and performed ERG immunohistochemistry, a next‐generation sequencing assay targeting recurrent gene fusions, and fluorescence in situ hybridization (FISH) for ERG and BRAF. Divergent differentiation included: sarcomatoid (n=10), adenosquamous (n=7), and pleomorphic giant cell carcinoma (n=7). Five patients had more than one variant. Four had variants only in metastases. ERG rearrangement was detected in 9 (47%, 7 via sequencing, showing TMPRSS2‐ERG and one GRHL2‐ERG fusion, and 2 via FISH, showing rearrangement via deletion). Of these, ERG immunohistochemistry was positive in the adenocarcinoma for 8/9 (89%) but only 5/9 (56%, typically decreased) in the variant. One patient had false‐positive ERG immunohistochemistry in the sarcomatoid component despite negative FISH. Two (11%) harbored BRAF fusions (FAM131A‐BRAF and SND1‐BRAF).
Conclusions
ERG gene fusions are present in these rare prostate cancer variants with a close frequency to conventional prostate cancer (9/19, 47%). ERG immunohistochemistry usually detects rearrangement in the adenocarcinoma but is less sensitive for the variant histology with weak to negative staining. Adenosquamous and sarcomatoid variants particularly can occur together. Molecular assessment may be an additional tool in select cases to confirm prostatic origin of unusual tumors. The presence of 2 BRAF gene rearrangements suggests that this gene fusion may be enriched in this setting, as RAF kinase fusions have been previously reported in 1‐2% of prostate cancers
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Growth Rates of Infants Randomized to Continuous Positive Airway Pressure or Intubation After Extremely Preterm Birth.
Objective To evaluate the effects of early treatment with continuous positive airway pressure (CPAP) on nutritional intake and in-hospital growth rates of extremely preterm (EPT) infants. Study design EPT infants (240/7-276/7 weeks of gestation) enrolled in the Surfactant Positive Airway Pressure and Pulse Oximetry Trial (SUPPORT) were included. EPT infants who died before 36 weeks of postmenstrual age (PMA) were excluded. The growth rates from birth to 36 weeks of PMA and follow-up outcomes at 18-22 months corrected age of EPT infants randomized at birth to either early CPAP (intervention group) or early intubation for surfactant administration (control group) were analyzed. Results Growth data were analyzed for 810 of 1316 infants enrolled in SUPPORT (414 in the intervention group, 396 in the control group). The median gestational age was 26 weeks, and the mean birth weight was 839 g. Baseline characteristics, total nutritional intake, and in-hospital comorbidities were not significantly different between the 2 groups. In a regression model, growth rates between birth and 36 weeks of PMA, as well as growth rates during multiple intervals from birth to day 7, days 7-14, days 14-21, days 21-28, day 28 to 32 weeks PMA, and 32-36 weeks PMA did not differ between treatment groups. Independent of treatment group, higher growth rates from day 21 to day 28 were associated with a lower risk of having a Bayley-III cognitive score Conclusions EPT infants randomized to early CPAP did not have higher in-hospital growth rates than infants randomized to early intubation