Ugur Mungan

Prognostic Significance of Microvascular Invasion in Localized Renal Cell Carcinoma

Objectives: The treatment of localized and even advanced renal cell carcinoma (RCC) is radical nephrectomy. However, 30% of these patients progress after radical nephrectomy. Prognostic factors are needed in order to determine the course of disease in patients undergoing radical nephrectomy. The aim of this study is to study the prognostic significance of microvascular invasion (MVI) in patients who had undergone radical nephrectomy for localized RCC.Methods: Between June 1989 and February 1999, pathologic sections of the specimens from 41 patients without metastases, nodal involvement or macroscopic venous involvement were investigated for MVI.Results: MVI was observed in 17% of the patients. MVI was related to the grade of the tumor and tumor size (p = 0.032, p = 0.017). In sarcomatoid–type RCC, MVI was more common than in other histologic types (p = 0.003). After a median follow–up of 48 months, the progression rate was 29% in patients with MVI and 17% without MVI (p = 0.001). Median progression time was 3 months in those with MVI and 41 months with no MVI (p = 0.01). The survival rate decreased from 85 to 70% in patients with MVI during a median follow–up of 48 months (p = 0.031). In multivariate analysis, MVI was not found to be an independent prognostic factor.Conclusion: Although MVI is closely related to progression and prognosis, in multivariate analysis it was not found to be an independent prognostic factor in localized RCC. We conclude that MVI should also be evaluated together with tumor grade in predicting the prognosis of patients with localized RCC.

Significance of P-glycoprotein, p53, and survivin expression in renal cell carcinoma.

OBJECTIVES This study addresses the relationship between cell cycle control protein p53, apoptosis inhibitor gene survivin, and chemotherapy resistance protein P-glycoprotein (P-gp) expression, and their prognostic impact in renal cell carcinoma (RCC). METHODS A group consisting of 104 patients with RCC was included from a predefined period of time. The median follow-up was 46 months. Tumor stage was defined according to the 2002 Tumor-Node-Metastasis staging system, and Fuhrman nuclear grading was used. Expression of p53, survivin, and P-gp was assessed on immunohistochemically stained slides of the representative blocks of the tumors. RESULTS A significant relationship was found between survival and histologic subtype (P = 0.001), tumor stage (P = 0.011), and tumor grade (P < 0.001). Although there was inverse correlation between p53 expression and stage (P = 0.014) and grade (P = 0.04), no correlation was observed with the histopathologic type or survival. There was no correlation between survivin expression and histologic subtype, stage, or survival, but there was a significant inverse correlation between survivin expression and tumor grade (P = 0.018). No significant correlation was found between any parameters tested, and P-gp expression. CONCLUSIONS Survivin, P-gp, and p53 expression do not play a role in prognosis of RCC. Our results suggest that survivin expression may be positively regulated by mutant p53 in RCC, and this expression may have an impact on resistance to chemotherapy in RCC.

Expression of p53 and mdm2 and Their Significance in Recurrence of Superficial Bladder Cancer

The purpose of this study is to evaluate the expression of p53 and mdm2 and to determine whether they may be used as additional predictors of recurrence in superficial transitional cell carcinoma of the bladder. Paraffin sections of 80 patients with superficial transitional cell carcinoma of the bladder, who were treated with transurethral resection, were stained with p53 and mdm2 antibodies using the standard avidin biotin immunoperoxidase method. Nuclear staining for both p53 and mdm2 was calculated as the percentage of labeled nuclei out of a total number of tumor cells counted. The percentage of p53- and mdm2-positive cells showed a significant relationship with tumor grade and recurrence (p = 0.002 and p = 0.016; p = 0.01 and p = 0.003, respectively). In addition, a weak inverse relationship was found between p53 and mdm2 values (r = -0.184). p53 and mdm2 reactivities are valuable parameters in predicting recurrence in superficial bladder cancer. Thus, mdm2 expression appears to play a role in predicting biologic behavior in superficial transitional carcinoma of the bladder.

Does angiogenesis predict recurrence in superficial transitional cell carcinoma of the bladder

OBJECTIVES To investigate the role of angiogenesis in predicting tumor recurrence and its correlation with established clinicopathologic prognostic factors in superficial transitional cell carcinoma of the bladder. METHODS The paraffin sections of 80 superficial papillary transitional cell bladder carcinoma specimens were stained with CD31 antibody to label the vascular endothelium using the standard streptavidin-biotin-immunoperoxidase method. The vascular surface density (VSD) equivalent to the vascular surface area per unit of tissue volume and number of vessels per square millimeter of stroma (NVES) were assessed by means of stereology, and these morphometric parameters of angiogenesis were statistically analyzed to interpret the relation to tumor recurrence in addition to tumor stage, grade, size, and number and the presence of carcinoma in situ. RESULTS VSD and NVES values showed no statistically significant difference between pTa and pT1 tumors or patients with and without recurrence. In contrast, VSD and NVES values were found to increase in higher grade tumors (P = 0.019). VSD values were also higher in patients with coexisting carcinoma in situ in pTa tumors (P <0.001). Tumor number and size and recurrence number and time to the first recurrence did not correlate with any vascular parameters. CONCLUSIONS Stereologic assessment of angiogenesis does not help to predict recurrence in superficial bladder cancer. Angiogenic parameters appeared to be well correlated with the conventional histologic grading system. Otherwise, the present study did not show any correlation of angiogenesis with any potential prognostic factors. This may be due to the diverse angiogenic pathways occurring in invasive and superficial tumors.

Proliferative activity, angiogenesis and nuclear morphometry in renal cell carcinoma

Abstract Background: Prognostic parameters other than tumor stage and grade are essential for renal cell carcinoma (RCC) patients. This study was undertaken to determine the usefulness of cellular proliferation, angiogenesis and nuclear morphometry in predicting the biological aggressiveness of RCC.

Echo contrast-enhanced power Doppler ultrasonography for assessment of angiogenesis in renal cell carcinoma.

Tumoral growth is an angiogenesis‐dependent event. Although there are studies about the importance of histopathologic angiogenesis in various malignancies, the assessment of the angiogenesis by radiologic techniques is not well established. The aim of this study was to investigate the efficacy of echo contrast‐enhanced power Doppler ultrasonography (PDUS) in determining the angiogenic status of renal cell carcinoma (RCC).

Giant angiomyolipoma associated with marked pulmonary lesions suggesting lymphangioleiomyomatosis in a patient with tuberous sclerosis

The association between Tuberous Sclerosis (TS) and Angiomyolipoma (AML) is well known. A patient with TS and giant AML mimicking Renal Cell Carcinoma (RCC), measuring 29 × 18 × 11 cm, weighing 4700 gr is presented. Imaging studies revealed coexistent pulmonary lymphangioleiomyomatosis and concurrent renal and pulmonary involvement is extremely rare in patients in TS. We believe that the growth potential of this hamartomatous lesion may reach to a life threatening size.

Expression of cathepsin D in bladder carcinoma: correlation with pathological features and serum cystatin C levels.

Aims and background The aim of this study is to evaluate the expression of cathepsin D in primary bladder cancer and to determine its relationship with conventional pathological features and serum cystatin C levels. Methods The immunohistochemical cathepsin D expression and staining patterns of epithelial and stromal cells were investigated in 21 patients with primary bladder carcinoma. Serum cystatin C levels were determined by immunoturbidimetry and compared with matched controls. Results There were 7 papillary neoplasms of low malignant potential, 7 low-grade and 7 high-grade carcinomas. Six tumors were invasive. Statistical analysis showed a significant inverse relationship between cathepsin D expression of the tumor cells and tumor grade and stage (P = 0.018 and P = 0.046, respectively). Serum cystatin C levels of the controls and patients varied between 0.39 mg/L and 1.99 mg/L (P >0.05). There was no significant relation between cathepsin D expression in tumor tissue and serum cystatin C levels. Conclusions Loss of cathepsin D expression in bladder carcinomas may be associated with high-grade and invasive tumors. Thus, increased cathepsin D expression by tumor cells may be related to local tumor invasion at an early stage, but it seems that extracellular cystatin C is not affected by cathepsin D expression of tumor or stromal cells, and cystatin C concentrations are not directly correlated with the progression of primary bladder carcinomas.

Prognostic significance of nuclear morphometry in renal cell carcinoma

Objective  To assess nuclear morphometry as a predictor of prognosis in patients with renal cell carcinoma (RCC).

Histologic grading of urothelial papillary neoplasms: impact of combined grading (two-numbered grading system) on reproducibility

The clinical management of tumor patients is often strongly infuenced by the tumor grade. The presence of heterogeneity is well recognized in a variety of tumors. Overall grade is based on highest grade area identified within a tumor. Urothelial carcinoma often contains different histological grades within the same tumor. This study investigates the impact of a combined grading system on the reproducibility of papillary urothelial neoplasms. A set prepared for an earlier study consisting of ten cases of each category (papillary urothelial neoplasm of low malignant potential (PUNLMP), LGPUC, and HGPUC) was used. Agreement between pairs of pathologists was evaluated using κ statistics for the combined scoring system. Interobserver agreement was fair to substantial as reflected by κ values ranging from 0.24 to 0.74 (mean κ = 0.43). The combined scores of 2 and 3 which included PUNLMP showed the lowest degree of agreement and when this category was excluded from the analysis, interobserver agreement increased significantly (mean κ = 0.65; ranging from 0.43 to 0.92) in terms of combined scores of 4, 5, and 6. PUNLMP has been shown to be the least reproducible component of a combined scoring system even among experienced observers. Exclusion of PUNLMP from grading scheme seems to improve interobserver variability.