Yen-Hwa Chang

Activation of the PI3K/Akt/mTOR pathway correlates with tumour progression and reduced survival in patients with urothelial carcinoma of the urinary bladder

Sun C‐H, Chang Y‐H & Pan C‐C
(2011) Histopathology58, 1054–1063
Activation of the PI3K/Akt/mTOR pathway correlates with tumour progression and reduced survival in patients with urothelial carcinoma of the urinary bladder

Prognostic significance of the 2004 WHO/ISUP classification for prediction of recurrence, progression, and cancer-specific mortality of non-muscle-invasive urothelial tumors of the urinary bladder: a clinicopathologic study of 1,515 cases.

To verify prognostic significance of the 2004 World Health Organization (WHO)/International Society of Urological Pathology (ISUP) grading systems, we retrospectively studied the tumors of 1,515 patients who underwent transurethral resection of primary non-muscle-invasive urothelial tumors (pTa, 1,006 patients; pT1, 509 patients) confined to the bladder. Cases were classified according to the 2004 WHO/ISUP systems as 212 cases of papillary urothelial neoplasm of low malignant potential (PUNLMP), 706 low-grade papillary urothelial carcinomas (LPUCs), and 597 high-grade papillary urothelial carcinomas (HPUCs). PUNLMP showed the statistically significantly lowest recurrence cumulative incidence compared with the other tumor types. There were significant differences and trends for higher progression and cancer-specific mortality cumulative incidence in the following order: PUNLMP, LPUC, pTa HPUC, and pT1 HPUC. No differences of progression and cancer-specific mortality cumulative incidence were found between pTa and pT1 LPUC. Our study validates the usefulness of the 2004 WHO/ISUP system to classify urothelial tumors into prognostically distinct categories that would contribute to the design of therapeutic and monitoring strategies for patients with non-muscle-invasive bladder urothelial tumors.

Are There Useful CT Features to Differentiate Renal Cell Carcinoma From Lipid-Poor Renal Angiomyolipoma?

OBJECTIVE This study was an attempt to identify key CT features that can potentially be used to differentiate between lipid-poor renal angiomyolipoma and renal cell carcinoma (RCC). MATERIALS AND METHODS We conducted an analysis of patients who received nephrectomy or renal biopsy from 2002 to 2011 with suspected RCC. We included tumors smaller than 7 cm with a completed three-phase CT examination. A radiologist and a urology fellow, blinded to histopathologic diagnosis, recorded the imaging findings by consensus and compared the values for each parameter between lipid-poor angiomyolipoma, RCC subtypes, and RCC as a group. Multivariate logistic regression analysis was performed for each univariate significant feature. RESULTS The sample in our study consisted of 132 patients with 135 renal tumors, including 51 men (age range, 26-84 years; mean age, 57 years) and 81 women (age range, 29-91 years; mean age, 57 years). These tumors included 33 lipid-poor angiomyolipomas, 54 clear-cell RCC, 31 chromophobe RCC, and 17 papillary RCC. Multivariate analysis revealed four significant parameters for differentiating RCC as a group from lipid-poor angiomyolipoma (angular interface, p = 0.023; hypodense rim, p = 0.045; homogeneity, p = 0.005; unenhanced attenuation > 38.5 HU, p < 0.001), five for clear-cell RCC, two for chromophobe RCC, and one for papillary RCC. Lipid-poor angiomyolipoma and clear-cell RCC showed early strong enhancement and a washout pattern, whereas chromophobe RCC and papillary RCC showed gradual enhancement over time. CONCLUSION Specific CT features can potentially be used to differentiate lipid-poor renal angiomyolipoma from renal cell carcinoma.

Immunohistochemical and molecular genetic profiling of acquired cystic disease-associated renal cell carcinoma.

Aims:  Acquired cystic disease‐associated renal cell carcinoma (ACD‐associated RCC) is a unique neoplasm that specifically develops in the background of acquired cystic disease of the kidney. The aim was to analyse nine ACD‐associated RCCs from three patients to determine their immunohistochemical and molecular characteristics using immunohistochemistry, comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH).

Correlation between serum prostate specific antigen and prostate volume in Taiwanese men with biopsy proven benign prostatic hyperplasia.

PURPOSE We studied the correlation between serum prostate specific antigen and the volume of different zones of the prostate in Taiwanese men with biopsy proven benign prostatic hyperplasia. MATERIALS AND METHODS A total of 233 patients with a mean age of 71.4 years (range 42 to 89), serum prostate specific antigen less than 10 ng/ml and pathologically confirmed benign prostatic hyperplasia were enrolled in this study. Total prostate and transitional zone volumes were measured with transrectal ultrasonography. Peripheral zone volume was determined by subtracting transitional zone volume from total prostate volume. Correlations between patient age, total serum prostate specific antigen and the volume of each prostate zone were analyzed with the Pearson correlation coefficient. A linear regression model was used to determine the relationship between prostate specific antigen and prostate volume. The prostate specific antigen-prostate volume relationship in our patients was compared with published data on white and Japanese men. RESULTS Age did not significantly correlate with serum prostate specific antigen and prostate volume. Serum prostate specific antigen significantly correlated with the volume of each prostate zone. After log transformation the Pearson correlation coefficient between total prostate specific antigen and the volume of the whole prostate gland, the transitional zone and the peripheral zone were 0.369, 0.377 and 0.272, respectively (p <0.001). Taiwanese men had lower prostate volume per unit prostate specific antigen comparing with white men, while the prostate specific antigen-total prostate volume relationship between Taiwanese and Japanese men was similar. CONCLUSIONS In Taiwanese men with biopsy proven benign prostatic hyperplasia the volume of each prostate zone has significantly correlates with serum prostate specific antigen. The prostate specific antigen-total prostate volume relationship in Taiwanese men is different from that in white men. However, the prostate specific antigen-total prostate volume relationship between Taiwanese and Japanese men is similar.

Her2 amplification distinguishes a subset of non-muscle-invasive bladder cancers with a high risk of progression

Background Several studies have employed immunohistochemistry to detect Her2/neu overexpression in urothelial carcinomas, yielding a tremendous range of positive expression rates. Few studies have examined Her2 status in non-muscle invasive bladder cancer (NMIBC) using fluorescence in situ hybridisation (FISH). Aim To evaluate Her2 amplification in NMIBC (Ta/T1), to correlate the findings with recurrence and progression, and compare the Her2 status between primary and progressive tumours. Methods FISH and immunohistochemistry for Her2/neu were performed on tissue arrays consisting of 36 papillary urothelial neoplasms of low malignant potential (PUNLMPs), 190 low grade urothelial carcinomas (LG-UCs) and 178 high grade urothelial carcinomas (HG-UCs). 32 cases with specimens of both primary and progressive tumours (from Ta/T1 to T2–4) were included for comparative analyses. Results 16 HG-UCs (9.0%) showed Her2 gene amplification while none of the PUNLMPs and LG-UCs showed this aberration. There was 100% concordance in the status of Her2 amplification between primary and progressive lesions. Immunohistochemistry and FISH results were in closest agreement when overexpression was defined as 50% of tumour cells showing immunoreactivity. The cumulative incidences of recurrence and progression in Her2-amplified HG-UC were significantly higher than in those without amplification. Conclusions A subset of high-grade NMIBCs contain Her2 amplification and are associated with markedly aggressive behaviour. Her2 diagnostics are valuable for distinguishing patients who require diligent surveillance and would potentially benefit from anti-Her2 therapies.

Common variants at 8q24 are associated with prostate cancer risk in Taiwanese men.

Recently, independent genome‐wide scans have found multiple genetic variants at 8q24 to be associated with prostate cancer risk. This study was performed to determine whether two of the variants more strongly associated with prostate cancer risk in European and American populations, specifically rs16901979 and rs6983561, were also associated with prostate cancer risk in Taiwanese men.

Constructing prognostic model incorporating the 2004 WHO/ISUP classification for patients with non-muscle-invasive urothelial tumours of the urinary bladder

Aim To construct a prognostic model for recurrence-free survival (RFS), progression-free survival (PFS) and cancer-specific survival (CSS) for patients who have undergone transurethral resection of non-muscle-invasive (pTa/pT1) urinary bladder urothelial tumours. Methods 1366 patients who had undergone transurethral resection of primary non-muscle-invasive urothelial tumours (pTa, 891 patients; pT1, 475 patients) confined to the bladder were retrospectively studied. Tumours were classified according to the 2004 WHO/International Society of Urologic Pathology grading system. Kaplan–Meier and stepwise Cox regression models were applied, and 200 bootstrap resamples were used to generate survival estimates and 95% CIs. A nomogram was developed that incorporated significant variables predicting survival. Results RFS, PFS and CSS probabilities for non-muscle-invasive bladder urothelial tumours were calculated. Incorporating salient prognostic factors (tumour grade, pT stage, patient age, status of intravesical instillation), the model satisfactorily predicted PFS (concordance index=0.79) and CSS (concordance index=0.87). Conclusions Robust nomograms were created to predict PFS and CSS. These data provide an overall perspective of disease outcomes which may aid in developing individualised follow-up programmes.

Tamoxifen and colchicine-modulated vinblastine followed by 5-fluorouracil in advanced renal cell carcinoma: a phase II study

OBJECTIVES Chemotherapy resistance of renal cell carcinoma (RCC) has been attributed in large part to multidrug resistance (MDR). Reported MDR-modulated chemotherapy for RCC, however, has resulted in only marginal response benefits. In this study, the MDR-modulated effect of paired tamoxifen and colchicine on vinblastine and the possible additive effect of 5-fluorouracil (5-FU) were investigated in the treatment of advanced RCC. METHODS Chemotherapy was administered every 4 weeks with biweekly vinblastine (4 mg/m(2)/day, intravenously on days 1 and 15) modulated by oral tamoxifen (100 mg/day) and colchicine (1 mg/day) from days -1 to 2 and from days 13 to 16. 5-FU (800 mg/m(2)/day from days 2 to 5) was administered after vinblastine administration as a continuous infusion. RESULTS Of 17 eligible patients with advanced RCC available for evaluation, 1 achieved a complete response (CR) and 3 a partial response (PR), with an overall response (CR plus PR) rate of 23.5%. The median overall survival time of all patients was 10 months (95% confidence interval [CI] 3.5 to 16.5); that of our patients with poor, intermediate, and favorable risks as stratified by Motzers model was 6 (95% CI 1.7 to 10.3), 10 (95% CI 7.9 to 12.2), and 26 (95% CI 24.4 to 27.6) months, respectively. These results are encouraging in view of the poor efficacy of chemotherapy in RCC observed previously. Additionally, the treatment toxicity was limited: toxicity of grade 3 or greater occurred in only 1 patient with leukopenia, and no treatment-related mortality was found. CONCLUSIONS The encouraging response rates and overall survival with limited toxicity warrant further investigation of this combination therapy as an integrated part of immunochemotherapy for RCC.

XP11.2 Translocation renal cell carcinoma: Clinical experience of Taipei Veterans General Hospital

Background: Xp11.2 translocation renal cell carcinoma (RCC), a recently recognized distinct subtype of RCC, is characterized by various translocations, all involving the TFE3 transcription factor gene. These rare cancers occur predominantly in children and young adults and comprise about one‐third of pediatric RCCs. In the present study, we review the clinical course of Xp11.2 translocation renal cell carcinoma in our institution. Methods: We identified eight cases with Xp11.2 translocation RCC between 2007 and 2010 from the pathological archives of the Taipei Veterans General Hospital. We retrospectively analyzed the patients’ characteristics, clinical manifestations, and specific pathological features for definitive diagnosis, surgical and systemic treatment and clinical outcome of these rare cancers. Results: Patients were aged 20 years to 49 years (mean age 28 years) with female predominance (6 females, 2 males). One patient presented with asymptomatic renal mass detected incidentally during abdominal sonography. Four patients complained of flank or abdominal pain, and the other three complained of gross hematuria at initial presentation. The mean tumor size was 9.2 cm (range, 4 cm–17 cm). Seven patients underwent radical nephrectomy for the primary tumor, while one presented with multiple metastases. All cases were confirmed by TFE3 immunohistochemistry, a sensitive and specific marker of tumors with TFE3 gene fusion, which showed positive nuclear staining. Three patients presented initially with metastatic diseases, and another three patients progressed to lung, liver and bone metastases at eight, seven and nine months postoperatively. Conclusion: Although RT‐PCR and DNA sequencing are the final diagnoses of the molecular identity of Xp11.2 translocation RCC, experienced pathologists could confirm the histologic diagnosis based on the distinctive morphologic features with positive TFE3 immunochemical nuclear stain. Surgical resection is the only treatment. The role of systemic therapy for local recurrence and metastasis remains to be determined.