The AR is expressed in normal breast tissue, and expression decreases with advancement to DCIS and invasive cancer. AR-positive TNBC was more common in older patients and had a higher propensity for LN metastases. AR-positive TNBC may represent a breast cancer subtype with unique features that may be amenable to treatment with alternative targeted therapies.
Mutations in SETD2, a histone H3 lysine trimethyltransferase, have been identified in clear cell renal cell carcinoma (ccRCC); however it is unclear if loss of SETD2 function alters the genomic distribution of histone 3 lysine 36 trimethylation (H3K36me3) in ccRCC. Furthermore, published epigenomic profiles are not specific to H3K36me3 or metastatic tumors. To determine if progressive SETD2 and H3K36me3 dysregulation occurs in metastatic tumors, H3K36me3, SETD2 copy number, or SETD2 mRNA abundance was assessed in two independent cohorts: metastatic ccRCC (n=71) and The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma dataset (n=413). Although SETD2 copy number loss occurs with high-frequency (>90%), H3K36me3 is not significantly impacted by monoallelic loss of SETD2. H3K36me3-positive nuclei were reduced an average of ∼20% in primary ccRCC (90% positive nuclei in uninvolved vs 70% positive nuclei in ccRCC) and reduced by ∼60% in metastases (90% positive in uninvolved kidney vs 30% positive in metastases) (P<.001). To define a kidney-specific H3K36me3 profile, we generated genome-wide H3K36me3 profiles from four cytoreductive nephrectomies and SETD2 isogenic RCC cell lines using chromatin immunoprecipitation (ChIP) coupled with high-throughput DNA sequencing and RNA sequencing. SETD2 loss of methyltransferase activity leads to regional alterations of H3K36me3 associated with aberrant RNA splicing in a SETD2 mutant RCC and SETD2 knockout cell line. These data suggest that during progression of ccRCC, a decline in H3K36me3 is observed in distant metastases, and regional H3K36me3 alterations influence alternative splicing in ccRCC.
Digital ureteroscopes are the latest trend in the evolution of endourology. It appears that a disposable ureteroscope may be cost beneficial at centers with a lower case volume per year. However, institutions with a high volume of cases may find reusable ureteroscopes cost beneficial.
Purpose
Currently, there is no reliable tool to predict response to intravesical bacillus Calmette-Guérin (BCG). Based on the fact that BCG is a Th1-polarizing immunotherapy, we attempt to correlate the pretreatment immunologic tumor microenvironment (Th1 or Th2) with response to therapy.
Materials and methods
Bladder cancer patients with initial diagnosis of carcinoma in situ (Tis) were stratified based on their response to BCG treatment. A total of 38 patients met inclusion criteria (20 patients who responded and 18 patients who did not respond). Immunohistochemical (IHC) methods known to assess the type of immunologic microenvironment (Th1 vs. Th2) were performed on tumor tissue obtained at initial biopsy/resection: the level of tumor eosinophil infiltration and degranulation (Th2 response); the number of tumor-infiltrating GATA-3+ (Th2-polarized) lymphocytes; and the number of tumor-infiltrating T-bet+ (Th1-polarized) lymphocytes. Results obtained from these metrics were correlated with response to treatment with BCG immunotherapy.
Results
The IHC metrics of the tumor immune microenvironment prior to BCG treatment were each statistically significant predictors of responders (R) vs. nonresponders (NR). Eosinophil infiltration and degranulation was higher for R vs. NR: 1.02±0.17 vs. 0.5±0.12 (P = 0.01) and 1.1±0.15 vs. 0.56±0.15 (P = 0.04), respectively. Ratio of GATA-3+ (Th2-polarized) lymphocytes to T-bet+ (Th1-polarized) lymphocytes was higher for R vs. NR: 4.85±0.94 vs. 0.98±0.19 (P<0.001). The 3 markers were combined to create a Th2 signature biomarker, which was a statistically significant (P<0.0001) predictor of R vs. NR. All IHC markers demonstrated that a preexisting Th1 immunologic environment within the tumor was predictive of BCG failure.
Conclusion
The Th1 vs. Th2 polarization of bladder tumor immune microenvironment prior to treatment with BCG represents a prognostic metric of response to therapy. If a patient has a preexisting Th1 immunologic response within the tumor, there is no value in using a therapy intended to create a Th1 immunologic response. An algorithm integrating 3 IHC methods provided a sensitive and specific technique that may become a useful tool for pathologists and urologists to predict response to BCG in patients with carcinoma in situ of the bladder.
Objective• To present the first age-stratified assessment of outcomes after holmium laser enucleation of the prostate (HoLEP) for the treatment of lower urinary tract symptoms resulting from prostate enlargement.
Patients and Methods• We retrospectively analysed and compared the morbidity, and the peri-operative and functional outcomes of patients aged 50-59, 60-69, 70-79 and Ն80 years. Complications at 30 days were stratified using the Clavien system. • Functional outcomes were assessed using the International Prostate Symptom Score (IPSS), maximum urinary flow rate (Qmax), post-void residual urine volume (PVR) and urinary continence.
Results• A total of 311 patients underwent HoLEP for obstructive voiding symptoms from August 2007 to June 2011, of whom 22 patients were aged 50-59 years, 91 were aged 60-69 years, 153 were aged 70-79 years, and 45 were aged Ն80 years.• The overall morbidity rates were similar among the age groups (20, 24.4, 21.6 and 22.1% for groups 1, 2, 3 and 4, respectively), as were the incidence of significant complications (Clavien grade Ն III), change in serum haemoglobin level, and length of hospital stay.• Patients Ն80 years did have a longer catheterization time (3.4 days) than patients aged 50-59 years (1.68 days).• By 1 year there were no significant differences in urinary continence, IPSS, Qmax, or PVR among the age groups.
Conclusions• Overall morbidity, hospital stay, and 1-year functional outcomes of HoLEP were similar among all age groups. • This study shows that HoLEP is a safe and effective treatment for benign prostatic hyperplasia regardless of age.
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