OBJECTIVE: This study investigated UTX and JMJD3 protein expression patterns in UC and assess their clinical significance.
PATIENTS AND METHODS: Immunohistochemistry (IHC) method was performed on formalin-fixed paraffin-embedded (FFPE) of UC tissues and compared to the normal bladder tissues from the autopsy specimen. The staining intensity of FFPE tissues were captured with the nuclear and overall positive pixels quantified using Aperio ImageScope software.
RESULTS: JMJD3 protein uptake was present in both nucleus and cytoplasm but UTX protein was predominantly seen in the cytoplasm of UC tissue. UTX was under expressed whereas JMJD3 was over expressed in UC compared to normal bladder. UTX and JMJD3 were not related to clinical stage and grade. However, significant association between JMJD3 expression and invasiveness of tumour (p<0.05) was noted, especially in MIBC group (88.9%). UTX and JMJD3 did not yield any significance as prognostic factors for diseasespecific survival.
CONCLUSIONS: Low expression of UTX protein in UC may indicate possible loss of its tumour suppressor activity and higher JMJD3 protein expression may indicate oncogenic activity. Hence, JMJD3 protein could be a potential diagnostic biomarker in detecting bladder UC of higher stages. Further investigation needed to study the dysregulation of this protein expression with associated gene expression.
MATERIALS AND METHODS: A systematic online search was conducted according to PRISMA statement for publications reporting on UR after RC. From initial 802 results, 14 articles including 6169 patients were included finally after exclusion of ineligible studies.
RESULTS: The incidence rate of UR was 4.4% (1.3%-13.7%). It was significantly lower with neobladder diversion (odds ratio = 0.44, 95% CI: 0.24-0.79, P = 0.006). Muscle invasion (hazard ratio = 1.18, 95% CI: 0.86-1.62, P = 0.31), carcinoma in situ (hazard ratio 0.97, 95% CI: 0.64-1.47, P = 0.88), prostatic stromal involvement (hazard ratio = 2.26, 95% CI: 0.01-627.75, P = 0.78), and prostatic urethral involvement (hazard ratio = 2.04, 95% CI: 0.20-20.80, P = 0.55) have no significant effect on UR. Men displayed tendency toward higher incidence of UR (odds ratio = 2.21, 95% CI: 0.96-5.06, P = 0.06). Absence of recurrence displayed tendency toward better disease specific survival, yet not significant (hazard ratio = 0.84, 95% CI: 0.66-1.08, P = 0.17). These results are limited by the retrospective nature of the included studies.
CONCLUSION: Muscle invasion, carcinoma in situ and prostatic stromal or urethral involvement at time of RC have no significant effect on UR. Orthotopic neobladder is associated with a significant lower risk of UR after RC.
METHODS: Medical records of bladder tumour cases from 2005 till 2009 were retrospectively reviewed and tabulated.
RESULTS: A total of 83 cases were recorded. The incidence was highest among the Chinese (56.6%), followed by Malays (34.9%), Indians (6%) and other races (2.4%). The male-to-female ratio was 9.4:1. The median age was 65 years (range 30-91 years) and median duration of follow up was 17.2 months (range 2-60 months). The main histopathology was transitional cell carcinoma (TCC) (90.4%), followed by adenocarcinoma (6%), squamous cell carcinoma (1.2%), leiomyoma (1.2%) and myeloid sarcoma (1.2%). For the TCCs, 58.6% were superficial while 41.4% were muscle invasive, and 13.3% had nodal metastasis with distant metastasis in 8%. Of the total, 5.3% were papillary urothelial tumours of low malignant potential, 33.3% pTa, 20% pT1, 10.7% pT2, 12.0% pT3 and 18.7% pT4. Of the superficial tumours, 32.5% were high grade tumours. There were ten radical cystectomies performed for transitional cell carcinomas; two had neobladder reconstruction whereas the other eight had ileal conduits. All the adenocarcinomas and squamous cell carcinomas were treated by radiotherapy due to the advanced stage of the disease while the myeloid sarcoma received chemotherapy. Mean survival of patients with muscle invasive cancer was 33+/-5 months. By the end of the study, 18.1% of patients had died of their cancer.
CONCLUSION: The incidence of bladder tumours is highest among the Chinese. When compared to other studies, the incidence of muscle invasive and high-grade superficial tumours was greater.
Methods: A total of 100 formalin-fixed paraffin-embedded urothelial carcinoma tissues were selected from the Department of Pathology, Hospital Kuala Lumpur and the protein expression of ISL1 and LHX5 was determined using immunohistochemistry.
Results: Positive expression of ISL1 and LHX5 was detected in 94% and 98% of the samples, respectively. There were no distinct LHX5 expression patterns associated with different cancer stages, but the proportion of high-expressing tumours was higher in high-grade tumours. In addition, there was a significant association between the expression of LHX5 and tumour grade. The proportion of tumours expressing high levels of ISL1 was found to be highest in later stage tumours.
Conclusion: The high percentage of tumours expressing both these genes suggests that ISL1 and LHX5 play an important role in bladder tumourigenesis across multiple stages.
MAIN METHODS: The expression of AR, 5α-reductase type1 (5αR1) and 5α-reductase type2 (5αR2) were examined in the bladder cancer cell line T24 and surgical pathology specimens. We also evaluated the status of androgen related cell proliferation and migration using the potent, non-aromatizable androgen agonist 5α-dihydrotestosterone (DHT).
KEY FINDINGS: DHT treatment significantly increased AR mRNA expression level, but not those of 5αR1 and 5αR2 in T24 cells. DHT also suppressed cellular migration with weaker and opposite effects on cell proliferation. A significant inverse correlation was detected between pT stage and AR, 5αR1 and 5αR2 immunoreactivity.
SIGNIFICANCE: Inverse correlations detected between tumor grade and AR/androgen metabolizing enzyme also suggested that the loss of AR and androgen-producing enzymes could be associated with tumor progression. Effects of DHT on cells also suggest that androgens may regulate cellular behavior.