• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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• pp.9137-9142
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• 2014

Background: To explore the expression of DcR3 protein and its clinicopathological significance in bladder urothelial carcinomas (BUC). Materials and Methods: Immunohistochemistry was performed to detect the expression of DcR3, caspase-3, Bcl-2, VEGF, Ki-67, PCNA and P53 in 166 BUC and 56 normal bladder tissues. Western blotting was used to detect the expression of DcR3 in the supernatants of cultured BUC cells. Results: Overexpression of DcR3 was found in BUC tissues and cell lines, with significant elevation as compared to normal bladder tissues (p<0.0001). Higher DcR3 expression was related to the status of invasion, lymph node metastasis and recurrence. Furthermore, DcR3 expression was negatively correlated with caspase-3 and positively associated with Bcl-2, VEGF, Ki-67 labeling index (LI), PCNA LI and P53 (all p<0.0001), respectively. Conclusions: DcR3 may play a crucial role as an oncogene in tumorigenesis, deterioration and progress of BUC via influencing related pathways of apoptosis, proliferation and angiogenesis. The detection of DcR3 protein in the formalinfixed and paraffin-embedded samples could assist to predict in prognosis of BUC patients.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.15
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• pp.6283-6286
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• 2014

In patients with microscopic hematuria there is a need for better identification of those who are at greater risk of harbouring bladder tumors. The RisikoCheck(C) questionnaire has a strong correlation with the presence of urothelial carcinoma (UC) of the bladder and in combination with other available tests may help identify patients who require detailed clinical investigations due to increased risk of presence of bladder tumors. This study aimed to evaluate the efficacy of RisikoCheck(C) questionnaire together with NMP-22(R) (BladderChek(R)) as a point-of-care urine test in predicting the presence of bladder tumors in patients presenting with microscopic hematuria as the sole finding. In this multi-institutional prospective evaluation of 303 consecutive patients without a history of urothelial carcinoma (UC), RisikoCheck(C) risk group assessment, urinary tract imaging and cystourethroscopy as well as urine cytology and Nuclear Matrix Protein-22 (NMP-22 BladderChek) testing were performed where available. The sensitivity, specificity, negative predictive value (NPV), and positive predictive values (PPV) for the risk adapted approach were calculated. All patients underwent cystoscopy, and tumors were detected in 18 (5.9%). Urine cytology and NMP-22 was positive for malignancy in 9 (3.2%) and 12 (7.5%) of patients, respectively. A total of 43 (14%) patients were in the high risk group according to the RisikoCheck(C) questionnaire. The sensitivity and specificity of the questionnaire in detecting a bladder tumor was 61.5 % and 84.0 % in the high risk group. In patients with either a positive NMP-22 test or high risk category RisikoCheck(C), 23.6% had bladder tumors with a corresponding sensitivity of 54.2% and specificity of 88.6%. If both tests were negative only 3.3% of the patients had bladder tumors. The results of our study suggest that the efficacy of diagnostic evaluation of patients with microscopic hematuria may be further enhanced by combining RisikoCheck(C) questionnaire with NMP-22.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.2251-2255
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• 2014

Background: The aim of this study was to evaluate 10 years of false positive urine cytology records, along with follow-up histologic and cytologic data, to determine the significance of suspicious urine cytology findings. Materials and Methods: We retrospectively reviewed records of urine samples harvested between January 2002 and December 2012 from voided and catheterized urine from the bladder. Among the 21,283 urine samples obtained during this period, we located 1,090 eligible false positive findings for patients being evaluated for the purpose of confirming urothelial carcinoma (UC). These findings were divided into three categories: atypical, indeterminate, and suspicious of malignancy. Results: Of the 1,090 samples classified as false positive, 444 (40.7%) were categorized as atypical, 367 (33.7%) as indeterminate, and 279 (25.6%) as suspicious of malignancy. Patients with concomitant UC accounted for 105 (23.6%) of the atypical samples, 147 (40.1%) of the indeterminate samples, and 139 (49.8%) of the suspicious of malignancy samples (p<0.0001). The rate of subsequent diagnosis of UC during a 1-year follow-up period after harvesting of a sample with false positive urine cytology initially diagnosed as benign was significantly higher in the suspicious of malignancy category than in the other categories (p<0.001). The total numbers of UCs were 150 (33.8%) for atypical samples, 213 (58.0%) for indeterminate samples, and 199 (71.3%) for samples categorized as suspicious of malignancy. Conclusions: Urine cytology remains the most specific adjunctive method for the surveillance of UC. We demonstrated the clinical value of dividing false positive urine cytology findings into three categories, and our results may help clinicians better manage patients with suspicious findings.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3223-3227
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• 2015

Objective: We evaluated the association of body mass index (BMI) with perioperative outcomes in patients who underwent laparoscopic or open radical nephroureterectomy. Materials and Methods: This retrospective single-center study included 113 patients who had been diagnosed with upper urinary tract cancer from January 1998 to June 2013 and were treated with laparoscopic nephroureterectomy (Lap group, n=60) or open nephroureterectomy (Open group, n=53). Laparoscopic nephroureterectomy was performed via a retroperitoneal approach following an open partial cystectomy. The two surgical groups were stratified into a normal-BMI group (<25) and a high-BMI group ($BMI{\geq}25$). The high-BMI group included 27 patients: 13 in the Lap group and 14 in the Open group. Results: Estimated blood loss (EBL) in the Lap group was much lower than that in the Open group irrespective of BMI (p<0.01). Operative time was significantly prolonged in normal-BMI patients in the Lap group compared to those in the Open group (p=0.03), but there was no difference in operative time between the Open and Lap groups among the high-BMI patients. Multivariate logistic regression analysis of the data for all the cohorts revealed that the open procedure was a significant risk factor for high EBL (p<0.0001, hazard ratio 8.02). Normal BMI was an independent predictor for low EBL (p=0.01, hazard ratio 0.25). There was no significant risk factor for operative time in multivariate analysis. There were no differences in blood transfusion rates or adverse event rates between the two surgical groups. Conclusions: Laparoscopic radical nephroureterectomy via a retroperitoneal approach can be safely performed with significantly reduced EBL even in obese patients with upper urinary tract cancer.

• BMB Reports
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• v.49 no.10
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• pp.578-583
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• 2016

Special AT-rich sequence binding protein 1 (SATB1) is a nuclear matrix-associated DNA-binding protein that functions as a chromatin organizer. SATB1 is highly expressed in aggressive breast cancer cells and promotes growth and metastasis by reprograming gene expression. Through genome-wide cross-examination of gene expression and histone methylation, we identified SATB1 target genes for which expression is associated with altered epigenetic marks. Among the identified genes, long noncoding RNA urothelial carcinoma-associated 1 (UCA1) was upregulated by SATB1 depletion. Upregulation of UCA1 coincided with increased H3K4 trimethylation (H3K4me3) levels and decreased H3K27 trimethylation (H3K27me3) levels. Our study showed that SATB1 binds to the upstream region of UCA1 in vivo, and that its promoter activity increases with SATB1 depletion. Furthermore, simultaneous depletion of SATB1 and UCA1 potentiated suppression of tumor growth and cell survival. Thus, SATB1 repressed the expression of oncogenic UCA1, suppressing growth and survival of breast cancer cells.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8293-8298
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• 2016

Background: Urinary stones are known predisposing factors for upper urinary tract carcinoma (UUTC) which are commonly detected at advanced stage with poor outcome because of rarity and lack of specific criteria for early detection. Aims and objectives: The main aim was to evaluate the impact of age, gender andstone characteristics on risk of developing UUTC in patients with chronic nephrolithiasis. We also discuss the role of aberrant angiogenesis (AA) and immunohistochemical expression of p53, p16INK4a, CK20 and Ki-67 in diagnosis of pelvicalyceal neoplastic (NL) and pre-neoplastic lesions (PNL) in these patients. Materials and Methods: Retrospective analysis of pelvicalyceal urothelial lesions from 88 nephrectomy specimens were carried out in a tertiary care centre from June 2012 to December 2014. Immunohistochemistry (IHC) was performed on 37 selected cases. Computed image analysis was performed to analyse aberrant angiogenesis. Results: All UUTC (5.7%) and metaplastic lesions were found to be associated with stones. Some 60% were pure squamous cell carcinoma and 40% were transitional cell carcinoma. Odd ratios for developing NL and PNL lesions in presence of renal stone, impacted stones, multiple and large stag horn stones were 9.39 (95% CI 1.15-76.39, p value 0.05), 6.28 (95% CI 1.59-24.85, p value 0.000) and 7.4 (95% CI, 2.29-23.94, p value 0.001) respectively. When patient age was ${\geq}55$, the odds ratio for developing NL was 3.43 (95% CI 1.19-9.88, p value 0.019). IHC analysis showed that mean Ki-67 indices were $3.15{\pm}3.63%$ for non-neoplastic lesions, $10.0{\pm}9.45%$ for PNL and $28.0{\pm}18.4%$ for NL. Sensitivity and specificity of CK20, p53, p16INK4a, AA were 76% and 95.9%; 100% and 27.5%; 100% and 26.5%; 92.3 % and 78.8% respectively. Conclusions: Age ${\geq}55years$, large stag horn stones, multiple stones and impacted stones are found to be associated with increased risk of NL and PNL in UUT. For flat lesions, a panel of markers, Ki 67 index >10 and presence of aberrant angiogenesis were more useful than individual markers.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.1755-1758
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• 2016

Background: Anemia is the most common hematologic abnormality in bladder cancer (BC) patients. We evaluated the impact of preoperative anemia on oncologic outcomes in BC undergoing transurethral resection of a bladder tumor (TURBT) for the first time diagnosis. Materials and Methods: We retrospectively evaluated the data collected from 639 patients who underwent TURBT between January 2006 and September 2014 in our department. Of these patients, 320 qualified for inclusion in the study. The primary efficacy endpoint was the effect of preoperative anemia status on cancer-specific and overall survival. Independent t-test and chi-square analyses were performed to assess the effects of anemia on oncologic outcomes. Survival was estimated by using the Kaplan-Meier test. Results: There were 118 (36.9%) and 202 (63.1%) patients in the anemia (Group-1) and non-anemia groups (Group-2), respectively. The median follow-up duration was 68 months. Anemia was associated with decreased overall survival (p<0.001). Comparison between cancer-specific survival of two groups did not show any statistically significant difference (p=0.17). Conclusions: Preoperative anemia status of BC patients according to World Health Organization classification is associated with decreased overall survival, but not with cancer-specific survival. We think that preoperative hemoglobin levels should be considered in patient counseling and decision-making for additional therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.6
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• pp.2787-2793
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• 2016

Background: Urinary bladder cancer is a common malignancy in the West and ranks as the $7^{th}$ most common cancer in our region of Kashmir, India. FGFR3 mutations are frequent in superficial urothelial carcinoma (UC) differing from the RAS gene mutational pattern. The aim of this study was to analyze the frequency and association of FGFR3 and RAS gene mutations in UC cases. Materials and Methods: Paired tumor and adjacent normal tissue specimens of 65 consecutive UC patients were examined. DNA preparations were evaluated for the occurrence of FGFR3 and RAS gene mutations by PCR-SCCP and DNA sequencing. Results: Somatic point mutations of FGFR3 were identified in 32.3% (21 of 65). The pattern and distribution were significantly associated with low grade/stage (p<0.05). The overall mutations in exon 1 and 2 in all the forms of RAS genes aggregated to 21.5% and showed no association with any clinic-pathological parameters. In total, 53.8% (35 of 65) of the tumors studied had mutations in either a RAS or FGFR3 gene, but these were totally mutually exclusive in and none of the samples showed both the mutational events in mutually exclusive RAS and FGFR3. Conclusions: We conclude that RAS and FGFR3 mutations in UC are mutually exclusive and non-overlapping events which reflect activation of oncogenic pathways through different elements.