Mazen A. Ghanem

Expression and prognostic relevance of vascular endothelial growth factor (VEGF) and its receptor (FLT-1) in nephroblastoma

Aims: To investigate the prognostic relevance of vascular endothelial growth factor (VEGF) and its receptor Flt-1 in nephroblastoma and whether tumour microvessel density (MVD) immunoreactivity, determined by the CD31 antigen, is related to the expression of VEGF and Flt-1. Methods: The expression of VEGF and Flt-1 and MVD were investigated by means of immunohistochemical analysis in 62 Wilms’s tumours. Patients were treated preoperatively with chemotherapy and had a mean follow up of 5.7 years. Results: In general, VEGF and Flt-1 were expressed in normal kidney parenchyma and to a variable extent in the three main components of Wilms’s tumour, namely: the blastemal, epithelial, and stromal cells. In tumour tissue, 52% and 47% of blastemal cells were positive for VEGF and Flt-1, respectively. A non-significant correlation was found between the expression of VEGF and Flt-1 in blastemal and epithelial cells and the clinicopathological stage. MVD was significantly higher in VEGF and Flt-1 positive tumours than in VEGF and Flt-1 negative tumours. Univariate analysis showed that the expression of VEGF and Flt-1 in blastemal cells was indicative of clinical progression and tumour specific survival. In addition, MVD expression was indicative of clinical progression. Epithelial staining was of no prognostic value. In a multivariate analysis, VEGF protein expression by blastemal cells was an independent prognostic marker for clinical progression. Conclusions: These results indicate that VEGF and Flt-1 protein expression are closely related to MVD and seem to be an important predictor for poor prognosis in treated patients with Wilms’s tumour. Therefore, the expression of these molecules in primary Wilms’s tumour may be useful in identifying those patients at high risk of tumour recurrence and in guiding antiangiogenic treatment.

The prognostic significance of apoptosis-associated proteins BCL-2, BAX and BCL-X in clinical nephroblastoma

Apoptotic cell death represents an important mechanism for the precise regulation of cell numbers in normal tissues. Various apoptosis-associated regulatory proteins, such as Bcl-2, Bax and Bcl-X, may contribute to the rate of apoptosis in neoplasia. The present study was performed to evaluate the prognostic value of these molecules in a group of 61 Wilms’ tumours of chemotherapeutically pre-treated patients using an immunohistochemical approach. Generally, Bcl-2, Bax and for Bcl-XS/L were expressed in the blastemal and epithelial components of Wilms’ tumour. Immunoreactive blastema cells were found in 53%, 41% and 38% of tumours for Bcl-2, Bax and for Bcl-XS/L, respectively. An increased expression of Bcl-2 was observed in the blastemal component of increasing pathological stages. In contrast, a gradual decline of Bax expression was observed in the blastemal component of tumours with increasing pathological stages. Also blastemal Bcl-XS/L expression decreased with stage. Univariate analysis showed that blastemal Bcl-2 expression and the Bcl-2/Bax ratio were indicative for clinical progression, whereas epithelial staining was of no prognostic value. Multivariate analysis showed that blastemal Bcl-2 expression is an independent prognostic marker for clinical progression besides stage. These findings demonstrate that alterations of the Bcl-2/Bax balance may influence the clinical outcome of Wilms’ tumour patients by deregulation of programmed cell death.

MIB-1 (KI-67) proliferation index and cyclin-dependent kinase inhibitor p27(Kip1) protein expression in nephroblastoma

Purpose: A number of studies have indicated that the tumor proliferation marker MIB-1 and cell cycle inhibitor p27Kip1 expression are of prognostic importance in a variety of cancers. The present study was performed to evaluate the prognostic value of these molecules in Wilms’ tumors. Experimental Design: MIB-1 and p27Kip1 expressions were investigated by the means of immunohistochemical analysis of 62 Wilms’ tumor. Patients were preoperatively treated by chemotherapeutic agents and had a mean follow-up of 5.7 years. Results: MIB-1 and p27Kip1 were expressed in normal kidney tissues and in the three main components of Wilms’ tumor, i.e., the blastemal, epithelial, and stromal cells. In Wilms’ tumors, the percentage of MIB-1-positive cells in the blastema ranged between 0 and 42% (mean, 9.4%) and in the epithelial component between 0 and 53% (mean, 19.9%), with a significant difference (P < 0.01). The percentage of blastemal p27Kip1-positive cells ranged between 3 and 85% (mean, 55.1%) and for the epithelial component between 1 and 87% (mean, 59%). There was a significant inverse relationship between blastemal MIB-1 and p27Kip1 expression in Wilms’ tumor. Univariate analysis showed that blastemal MIB-1 and p27Kip1 expression were indicative for clinical progression and tumor-specific survival. In a multivariate analysis, blastemal MIB-1 and p27Kip1 protein expression proved to be an independent prognostic for clinical progression besides stage. Conclusions: It was concluded that both MIB-1-based proliferative activity and p27Kip1 protein expression in the blastema have prognostic impact in Wilms’ tumor.

Expression and prognostic value of platelet-derived growth factor-AA and its receptor α in nephroblastoma

To investigate the potential role of platelet‐derived growth factor‐AA (PDGF‐AA) and the PDGF‐α receptor as prognostic markers in Wilms’ tumour.

Expression And Prognostic Value Of CD44 Isoforms In Nephroblastoma (Wilms Tumor)

PURPOSE CD44 is a group of transmembranous glycoproteins formed by alternative splicing of a single messenger RNA. An abnormal pattern of CD44 expression has been demonstrated in several human malignancies. We evaluate the prognostic value of standard CD44 (CD44s) and some of its isoforms in treating clinical Wilms tumor. MATERIALS AND METHODS The immunohistochemical expression of CD44 isoforms was studied in paraffin material of 61 clinical Wilms tumors. Patients were treated preoperatively with chemotherapy and mean followup was 5.7 years. RESULTS Generally CD44s, CD44v5 and CD44v10 were expressed in normal kidney tissues and at variable levels in the 3 cell types of Wilms tumor (blastemal, epithelial and stromal). No CD44v6 expression was found neither in normal kidney or in tumor tissue. CD44s, CD44v5 and CD44v10 epithelial expression gradually decreased from stage T1 to T3. By contrast the percentage of CD44 positive cells in the blastemal component significantly increased from T1 to T3. CD44 immunoreactive blastema cells were found in 62%, 44% and 41% for CD44s, CD44v5 and CD44v10, respectively. Blastemal expression of CD44s and CD44v5 statistically significantly correlated with clinicopathological stage. Univariate and multivariate analyses showed that blastemal CD44v5 expression was indicative of poor prognosis. CONCLUSIONS Increased expression of CD44v5 in the blastemal part of Wilms tumor correlated with tumor stage, clinical progression and tumor related death. Therefore, blastemal CD44v5 expression may be of value in identifying patients with a high propensity for distant metastases. These patients might benefit from adjuvant chemotherapy and/or radiotherapy.

The role of varicocele sclerotherapy in men with severe oligo-astheno-teratozoospermia

The aim of this study was to verify the role of antegrade scrotal sclerotherapy for the treatment of varicoceles in infertile men with severe oligo-astheno-teratozoospermia (OAT). The 59 patients with severe OAT in this study underwent antegrade scrotal sclerotherapy for the treatment of varicoceles. The outcome was assessed in terms of improvement in semen parameters and spontaneous conception rate. Semen parameters and reproductive hormones were evaluated before antegrade sclerotherapy (AS) and 6 months after AS. After an average follow-up time of 34.8±3.2 months, significant improvement was noted in the mean sperm concentration, motility and morphology in 36 patients (61%). Spontaneous pregnancy occurred in nine couples (15%). Six months after treatment, inhibin B levels were significantly higher (P<0.04), whereas follicle-stimulating hormone (FSH) levels were significantly lower (P<0.001) than before treatment. Antegrade internal spermatic vein sclerotherapy can significantly improve seminal parameters and hormonal parameters in men with severe OAT and may even result in spontaneous pregnancy in couples who would otherwise be candidates for intracytoplasmic sperm injection (ICSI).