KLRF1, a novel marker of CD56bright NK cells, predicts improved survival for patients with locally advanced bladder cancer.

BACKGROUND: Bladder tumor-infiltrating CD56bright NK cells are more tumor cytotoxic than their CD56dim counterparts. Identification of NK cell subsets is labor-intensive and has limited utility in the clinical setting. Here, we sought to identify a surrogate marker of bladder CD56bright NK cells and to test its prognostic significance. METHODS: CD56bright and CD56dim NK cells were characterized with the multiparametric flow (n = 20) and mass cytometry (n = 21) in human bladder tumors. Transcriptome data from bladder tumors (n = 351) profiled by The Cancer Genome Atlas (TCGA) were analyzed. The expression levels of individual markers in intratumoral CD56bright and CD56dim NK cells were visualized in tSNE plots. Expressions of activation markers were also compared between Killer Cell Lectin-Like Receptor Subfamily F Member 1 (KLRF1)+ and KLRF1- NK cells. RESULTS: Intratumoral CD56bright NK cells displayed a more activated phenotype compared to the CD56dim subset. Multiple intratumoral cell types expressed CD56, including bladder tumor cells and nonspecific intratumoral CD56 expression was associated with worse patient survival. Thus, an alternative to CD56 as a marker of CD56bright NK cells was sought. The activation receptor KLRF1 was significantly increased on CD56bright but not on CD56dim NK cells. Intratumoral KLRF1+ NK cells were more activated and expressed higher levels of activation molecules compared with KLRF1- NK cells, analogous to the distinct effector function of NK cells across CD56 expression. High intratumoral KLRF1 was associated with improved recurrence-free survival (hazard ratio [HR] 0.53, p = 0.01), cancer-specific survival (HR 0.47, p = 0.02), and overall survival (HR 0.54, p = 0.02) on multivariable analyses that adjusted for clinical and pathologic variables. CONCLUSIONS: KLRF1 is a promising prognostic marker in bladder cancer and may guide treatment decisions upon validation.

Impact of anatomical and socioeconomic factors on timing of urological consultation for boys with cryptorchidism.

PURPOSE: Cryptorchidism is a common finding in infants and young boys. Early repair lessens the extent of testicular injury. We hypothesized that anatomical and socioeconomic factors affect the timing of consultation and treatment for boys with cryptorchidism. MATERIALS AND METHODS: Under an institutional review board approved protocol we reviewed the records at a single institution of children who underwent exploration for unilateral or bilateral cryptorchidism. Demographic and anatomical factors were recorded. RESULTS: The median age of 677 boys at consultation and surgery was 20.3 and 28.9 months, respectively. Median age at consultation for boys with nonpalpable and palpable testicles was 12.3 and 20.9 months, respectively (p = 0.03). Boys with a concomitant penile anomaly had a younger median age at consultation than boys without a penile anomaly (8.5 vs 20.3 months, p <0.01). Demographic factors did not vary with respect to time to consultation and surgery (p >0.05). Multivariate analysis showed that abdominal site and concomitant penile anomaly were associated with earlier time to consultation (p = 0.02 and <0.01, respectively). CONCLUSIONS: The timing of consultation for boys with undescended testicles does not vary in regard to race, language or insurance type at this tertiary care institution. Instead, anatomical factors influenced age at consultation for boys with cryptorchidism. This suggests that in some geographic regions access to care is not restricted for minorities or noncommercially insured children.

Ex-premature infant boys with hypospadias are similar in size to age-matched, ex-premature infant boys without hypospadias.

OBJECTIVE: Studies have postulated that hypospadias, prematurity, and low birth weight are linked by defects in androgen signaling. To determine whether premature, hypospadiac boys are small and remain so, we compared their size at birth and at hypospadias repair to premature boys who underwent post-neonatal circumcision. METHODS: We identified premature boys admitted to Texas Children's Hospital who underwent either hypospadias repair or circumcision after 4 months of age. Age, weight, and height at birth and surgery were recorded. RESULTS: Fifty-four boys had hypospadias and 34 did not. For hypospadiac boys, the mean birth weight and age, height, and weight at surgery were lower than for boys without hypospadias. More importantly, length-for-age and weight-for-age percentiles were also lower for hypospadiac boys. When subset analysis was performed on boys younger than 2 years at surgery, however, there were no significant differences in height or weight between hypospadiac and non-hypospadiac boys. CONCLUSION: Our series suggests that premature, hypospadiac boys are born smaller than age-matched, non-hypospadiac controls. However, there were no age-corrected size differences between hypospadiac and non-hypospadiac boys at surgery. This implies that hypospadiac boys exhibit post-neonatal 'rebound' growth. Global growth deficits, if any, do not persist in hypospadiac boys.