Noguchi S

c-erbb-2 gene amplification as a prognostic marker in human bladder cancer

OBJECTIVES To evaluate c-erbB-2 gene amplification and its prognostic significance in transitional cell carcinoma of the bladder. METHODS Alterations in the gene copy number of c-erbB-2 were detected in 57 bladder tumor samples using a method based on the polymerase chain reaction. RESULTS Eighteen tumors (32%) showed gene amplification of c-erbB-2, which correlated with tumor grade and stage. A strong association of c-erbB-2 amplification with patient survival was also found. The amplification resulted in a significantly poorer prognosis among the patients with high-grade and/or invasive tumors. Multivariate analysis revealed that c-erbB-2 amplification and tumor grade were independent prognostic factors. CONCLUSIONS Our data indicate a possible role of the c-erbB-2 gene in the development of aggressive behavior in bladder tumors. Moreover, the use of c-erbB-2 gene amplification, together with tumor grade and stage, could provide an accurate basis for determining the prognosis of bladder cancer.

Early assessment by FDG-PET/CT of patients with advanced renal cell carcinoma treated with tyrosine kinase inhibitors is predictive of disease course

BackgroundWe reported previously that 18F-2-fluoro-2-deoxyglucose positron emission tomography/ computed tomography (FDG PET/CT) had potential for evaluating early response to treatment by tyrosine kinase inhibitors (TKIs) in advanced renal cell carcinoma (RCC). This time we investigated the relation of the early assessment by FDG PET/CT to long-term prognosis with an expanded number of patients and period of observation.MethodsPatients for whom TKI treatment for advanced RCC was planned were enrolled. FDG PET/CT was performed before TKI treatment and after one month of TKI treatment. The relations of the FDGPET/CT assessment to progression free survival (PFS) and overall survival (OS) were investigated.ResultsThirty-five patients were enrolled (sunitinib 19 cases, sorafenib 16 cases). The patients with RCC showing high SUVmax in pretreatment FDG PET/CT demonstrated short PFS (P =0.024, hazard ratio 1.137, 95% CI 1.017-1.271) and short OS (P =0.004, hazard ratio 1.210 95% CI 1.062-1.379). Thirty patients (sunitinib 16 cases, sorafenib 14 cases) were evaluated again after 1 month. The PFS of the patients whose SUVmax decreased<20% was shorter than that of the patients whose SUVmax decreased<20% (P = 0.027, hazard ratio 3.043, 95% CI 1.134-8.167). The PFS of patients whose tumor diameter sum increased was shorter than that of the patient with tumors whose diameter sum did not (P =0.006, hazard ratio 4.555, 95% CI 1.543-13.448).The patients were classified into three response groups: good responder (diameter sum did not increase, and SUVmax decreased ≥ 20%), intermediate responder (diameter sum did not increase, and SUVmax decreased<20%), and poor responder (diameter sum increased, or one or more new lesions appeared). The median PFS of good, intermediate, and poor responders were 458 ± 146 days, 131 ± 9 days, and 88 ± 26 days (good vs. intermediate P = 0.0366, intermediate vs. poor P = 0.0097, log-rank test). Additionally the mean OSs were 999 ± 70 days, 469 ± 34 days, and 374 ± 125 days, respectively (good vs. intermediate P = 0.0385, intermediate vs. poor P = 0.0305, log-rank test).ConclusionsThe evaluation of RCC response to TKI by tumor size and FDG uptake using FDG PET/CT after 1 month can predict PFS and OS.

Prognostic Value of Ki-67 for Recurrence and Progression of Superficial Bladder Cancer

PURPOSE We retrospectively reviewed 104 cases of superficial bladder cancer to ascertain whether the Ki-67 labeling index predicts recurrence and progression. MATERIALS AND METHODS Archival specimens from superficial bladder cancer cases were immunostained with Ki-67. RESULTS The recurrence rate was significantly higher in cases with a Ki-67 labeling index of 5.35 or greater than in those with a value less than 5.35 (p < 0.001). The recurrence rate at 2 years was 70% in cases with a Ki-67 labeling index of 5.35 or greater and 22% in those with an index less than 5.35 (p < 0.001). Using multivariate analysis the index predicted recurrence of bladder cancer (p < 0.005). Median Ki-67 labeling index in cases with progression was significantly higher than in those without progression (p < 0.01). CONCLUSIONS The Ki-67 labeling index is an independent predictive factor for recurrence of superficial bladder cancer.

Spontaneous Rupture of Adrenal Pheochromocytoma: A Case Report

We report a case of retroperitoneal hemorrhage due to spontaneous rupture of a right adrenal pheochromocytoma, presenting as an acute abdominal emergency with symptoms of peripheral vasoconstriction. An elective operation was successfully performed on day 7 after sufficient volume replacement with continuous administration of an alpha and beta-adrenergic blocking agent.

RENAL ONCOCYTOMA CONTAINING “CHROMOPHOBE” CELLS

We report a rare case of renal oncocytoma containing occasional “chromophobe” cells. This case suggests an intimate relationship between oncocytoma and “chromophobe” renal cell carcinoma.

The Loss of Retinoblastoma Gene in Association with c-myc and Transforming Growth Factor-beta 1 Gene Expression in Human Bladder Cancer

PURPOSE We investigate the roles and possible interactions of the retinoblastoma, transforming growth factor-beta 1 and c-myc genes in bladder cancer. MATERIALS AND METHODS The expression of these 3 genes was examined in 38 biopsy specimens of human bladder cancer by immunohistochemical analysis or Northern blotting. RESULTS Loss of the retinoblastoma protein expression was most significantly correlated with high grade cancer. Over expression of c-myc or expression of transforming growth factor-beta 1 was less associated with tumor grade or stage, although c-myc over expression defined stage Ta against other stage tumors, since no stage Ta lesions had increased c-myc expression. Finally, loss of retinoblastoma gene function did not correlate with either c-myc or transforming growth factor-beta 1 expression. CONCLUSIONS These results further support that retinoblastoma gene inactivation is an important factor in the progression of bladder cancer, and suggest that transforming growth factor-beta 1 and c-myc are not regulators or are not regulated by retinoblastoma gene expression.

CYCLIN D1 PROTEIN OVEREXPRESSION IS RELATED TO TUMOR DIFFERENTIATION, BUT NOT TO TUMOR PROGRESSION OR PROLIFERATIVE ACTIVITY, IN TRANSITIONAL CELL CARCINOMA OF THE BLADDER

PURPOSE We attempted to clarify the significance of cyclin D1 in the development and progression of transitional cell carcinoma of the bladder in humans. MATERIALS AND METHODS Immunohistochemical staining of archival tissue specimens of transitional cell bladder carcinoma obtained from 163 patients was performed by the labeled streptavidin-biotin-peroxidase method. RESULTS Cyclin D1 protein overexpression was observed in 51 of the 163 specimens (31.3%). Cyclin D1 protein overexpression was showed a highly significant inverse correlation with the histological grade of malignancy (p < 0.01). Grade 3 tumors showed a highly significant low incidence of cyclin D1 protein overexpression as compared with grade 2 tumors (p < 0.01). There was no significant correlation between the overexpression of cyclin D1 protein and tumor stage or the Ki-67 labeling index. CONCLUSION Cyclin D1 in transitional cell bladder carcinoma was closely related to tumor differentiation but not to tumor progression. Transitional cell carcinoma of the bladder may utilize another pathway for proliferation that is independent of cyclin D1.

PROGNOSTIC SIGNIFICANCE OF KI-67 EXPRESSION IN TRANSITIONAL CELL BLADDER CARCINOMA AFTER RADICAL CYSTECTOMY

We evaluated the prognostic significance of the Ki-67 labeling index (Ki-67 LI) in 75 patients with transitional cell carcinoma of the bladder who underwent radical cystectomy. Immunohistochemical staining of archival material was performed by the streptavidin-biotin method. Univariate survival analysis showed that Ki-67 LI (p < 0.001), histologic grade (p < 0.05), tumor stage (p < 0.001) and the number of positive lymph nodes (p < 0.001) significantly correlated with prognosis. Multivariate survival analysis indicated that the Ki-67 LI (p < 0.05), histologic grade (p < 0.01), tumor stage (p < 0.01), presence of lymph node metastases (p < 0.05) and use of neo-adjuvant therapy (p < 0.05) had independent prognostic value. The Ki-67 LI is an independent prognostic factor for patients with transitional cell bladder cancer treated by radical cystectomy.

Prognostic significance of Ki-67, p53, and Bcl-2 expression in prostate cancer patients with lymph node metastases: a retrospective immunohistochemical analysis.

The prognostic significance of Ki‐67, p53, and Bcl‐2 expression was evaluated in prostate cancer patients with lymph node metastases. Immunohistochemical staining of archived material obtained from 56 patients was performed by the streptavldin‐biotin method. Univariate survival analysis showed that a Ki‐67 labeling index (Ki‐67 LI) of ≥8.4 in the primary tumor identified a group of patients with a significantly poorer prognosis (P<0.001). Furthermore, a Ki‐67 LI of ≥8.7 in the nodal metastatlc tumor was also associated with a poorer prognosis (P<0.01). Multivariate analysis showed that the Ki‐67 LI of primary tumors (P<0.01) and lymph node metastases (P<0.01) had independent prognostic value. p53 and Bcl‐2 expression had no prognostic value in patients with prostate cancer and lymph node involvement. The Ki‐67 LI has more prognostic value than p53 and Bcl‐2 expression for patients with prostate cancer that has spread to the lymph nodes.

Prognostic significance of Ki-67 labeling index in urothelial tumors of the renal pelvis and ureter.

PURPOSE We evaluated the prognostic significance of the Ki-67 labeling index in 70 patients with primary urothelial tumors of the renal pelvis and ureter. MATERIALS AND METHODS Immunohistochemical staining for Ki-67 in archival tumor materials was done by the streptavidin-biotin method. RESULTS Univariate survival analysis showed that the prognosis of patients with a high Ki-67 labeling index of 21.7 or more was significantly worse than that of patients with an intermediate labeling index of 13.3 to less than 21.7 (p < 0.01) or a low labeling index of less than 13.3 (p < 0.001). Multivariate survival analysis showed that staining for Ki-67 labeling index was significantly correlated with prognosis (p < 0.01). CONCLUSIONS Analysis of Ki-67 labeling index provides useful prognostic information about patients with primary urothelial tumors of the renal pelvis and ureter.