Prognostic value of proliferating cell nuclear antigen in Wilms' tumour in children.

AIMS: To evaluate the prognostic value of index Proliferating Cell Nuclear Antigen (PCNA) in Wilms' tumour in children. METHODS: The study comprised 64 children aged from 2 days to 13 years treated according to the SIOP (Society International of Oncology Paediatric) and accepted by the PPGGL (Polish Paediatric Group for the Treatment of Solid Tumours). The studies were conducted on tumour tissue removed during surgery, fixed in formalin and embedded in paraffin blocks. Sections (4 microns) were evaluated by immunohistochemistry, using the peroxidase method to determine the expression of PCNA in Wilms' tumour cells by primary monoclonal antibody NCL-PCNA from Novocastra. RESULTS: The percentage of immunopositive cells in particular fragments of the tumour ranged from 0--93%, mean 30.5%, median 25.5%. Mean and median values enabled division of children into two groups: Group A, where the percentage of cells staining with anti-PCNA was <30% and Group B, where this percentage was >30%. The expression of PCNA was evaluated in various stages of advancement, various histological types and depending on the course of disease. The studies revealed the correlation between index PCNA and stage of advancement P<0.01, index PCNA and histological type of Wilms' tumour P<0.025. Moreover we observed that deaths were found more frequently in tumours with index PCNA >30%, P<0.001. CONCLUSIONS: PCNA is a useful prognostic factor in Wilms' tumour in children.

Prognostic value of p53 expression in Wilms' tumor in children.

BACKGROUND: The aim of this report was to evaluate the prognostic value and clinical correlations of p53 expression in children with Wilms' tumor. MATERIAL AND METHODS: The study comprised 61 children aged from 2 days to 13 years (median 39 months), diagnosed and treated according to SIOP and PPGGL criteria in three centers co-operating with the PPGGL. The studies were conducted on tumor tissue removed during surgery, fixed in formalin and embedded in paraffin blocks. Then 4-micron sections were evaluated by immunohistochemistry, using the peroxidase method to determine the expression of p53 in Wilms' tumor cells by means of primary monoclonal antibody NCL-p53 from Novocastra. RESULTS: The percentage of immunopositive cells in particular fragments of the tumor ranged from 0% to 70% (mean 20.4%, median 16.0%). The mean and median values enabled the children to be divided into two groups: Group A, where the percentage of cells staining with anti-p53 antibody was >20% (23 cases), and Group B, where this percentage did not exceed 20%. The expression of p53 was then evaluated in various stages of advancement and various histological types, depending on the course of the disease. In Group A, tumors at higher stages of advancement stages were more frequent (p<0.05), and showed a higher degree of malignancy (p<0.06; EFS=56.53%). In Group B, lower stages of advancement were more frequent (p<0.05), the degree of malignancy was lower, and the EFS was 81.58%. A discrimination test, however, showed that the determination of p53 expression in Wilms' tumor cells has moderate sensitivity (58.825%), positive prediction (43.47%), and relatively high specificity (70.45%) and negative prediction (81.57%), which means that low indexes of p53 expression have higher prognostic value. CONCLUSIONS: The index of p53 expression is not an independent prognostic factor in Wilms' tumor in children, but this determination may be helpful in identifying high-risk and low-risk patients.

Multicenter retrospective analysis of various primary pediatric malignant hepatic tumors--management in a series of 47 Polish patients (1985-1995).

Forty-seven children treated in various Polish centers between 1985 and 1995 for primary malignant liver tumors were retrospectively analyzed. Hepatoblastoma (HB) prevailed--it was found in 39 cases. There were 6 hepatocarcinoma (HCC) cases and 2 cases of undifferentiated sarcoma (UDS). In 44% of HB patients the tumor involved both liver lobes. 18% of children with HB presented with pulmonary metastases at diagnosis. Chemotherapy was applied in 92% of cases (preoperatively in 67%). Tumor resection was performed in 56% of HB patients. Overall survival of patients with hepatoblastoma was 43.6%, while it was 50% for hepatocarcinoma and 100% for undifferentiated sarcoma (2 cases only). Mean observation time was 58 months. The hepatoblastoma subgroup, being the largest (83% of all cases), was analyzed separately for prognostic factors. Completeness of tumor excision strongly influenced survival. Involvement of both lobes of the liver and multifocality of the tumor were other adverse prognostic factors.

[Familial occurrence of nephroblastoma]. / Rodzinne wystepowanie nerczaka plodowego.

Wilms' tumour can develop in ways: sporadic--non-hereditary or familial. Familial Wilms' tumour is not very seldom. It is a form of autosomal dominant segregation and probably low and variable penetration. Up to now it has not been observed in the presence of characteristic genetic changes. Taking into consideration the case of the patient with positive family interview we presented the way of diagnosing and treating the child. Moreover we presented the results of cytogenetic examination and molecular analyses (loss of heterozygosity of WT1 gene and loss of heterozygosity 16 q), which had not shown any changes. We also discussed the actual level of knowledge abut familial form of Wilms' tumour.

16q heterozygosity loss in Wilms' tumour in children and its clinical importance.

INTRODUCTION: The loss of heterozygosity (LOH) of 16q is a structural change detected in about 20-30% of Wilms' tumour cases. Aberrations which result in deletion of 16q are also found in breast cancer, prostate cancer and liver cancer, where they are connected with a worse prognosis. The hypothesis of a bad prognosis in nephroblastomas with LOH 16q was first formulated by scientists from NWTS (National Wilms Tumor Study) on the basis of 232 cases of Wilms' tumour. However, SIOP studies (International Society of Paediatric Oncology) which included 28 cases of Wilms' tumour, did not show any clinico-pathological correlations with LOH 16q. Therefore, we aimed to evaluate the importance of LOH 16q in relation to clinico-pathological factors in a group of children, treated according to the SIOP criteria. AIMS: The aim of this work was to evaluate the frequency of LOH 16q in sporadic unilateral Wilms' tumour and to study the relationship between LOH 16q and selected patho-clinical parameters. The study comprised 66 children (31 girls and 35 boys) aged from 2 days to 13 years. METHODS: LOH 16q was studied by the examination of polymorphism of marker sequences in the region 16q24. DNA was isolated from paraffin sections of tissue for routine microscopic examination by the microdissection method. The method of study involved the amplification of polymorphic sequences from the 16q24 region by polymerase chain reaction (PCR) and separation of the products of amplification by polyacrylamide gel electrophoresis. The results were the subject of statistical analysis in relation to gender, age of child at first diagnosis, stage of clinical advancement and histological type of tumour. The connection between LOH 16q and recurrences, metastases and death, and failure free survival and absolute survival of children followed-up for over 24 months after nephrectomy were studied. RESULTS: The study revealed a lack of correlation between LOH 16q and gender, however LOH 16q was more frequent in children with Wilms' tumour aged >24 months, P<0.05. Also, LOH 16q was more frequent in tumours classified as clinical stage (CS) II or III than in CS I, P<0.05, but there were no differences in the occurrence of LOH 16q in tumours classified as CS II and CS III. We have found no correlation between LOH 16q and the histological type of tumour. However, LOH 16q has been found three times as frequently in tumours from children who died than in tumours of children who survived, P<0.0024.

Venoocclusive liver disease (VOD) as a complication of Wilms' tumour management in the series of consecutive 206 patients.

UNLABELLED: In 4 years (1993-1996) 206 pts. with nephroblastoma were treated. All children were treated according to SIOP 93-01 protocol. Overall survival was 92%. In 27 cases hepatotoxic events occurred. In 10 cases, venoocclusive liver disease (VOD) was diagnosed. VOD is a syndrome associated with hepatomegaly, sudden weight gain or ascites and jaundice. It results from damage to the endothelium of hepatic venules and necrosis of central hepatocytes with subsequent proliferation of fibrous tissue and occlusion of the central hepatic veins. Dactinomycin is one of the drugs considered responsible for its development. Mean age of VOD patients was 4 yrs, however 3 of them were below 1 yr. In all cases, VOD occurred during postoperative chemotherapy (mean 16 th week of treatment). All patients received dactinomycin and vincristine. Five children with right kidney tumors underwent post-operative abdominal irradiation. Main VOD symptoms were hepatomegaly and ascites (80%). Hypertransaminasaemia, as well as, on ultrasound, gallbladder wall thickening and/or free abdominal fluid were observed. Median VOD duration was 27 days and its course was usually temporary and self-limiting. However, in 2 cases recurrent VOD episodes were noted. All children received supportive treatment only. In 6 cases, VOD resulted in chemotherapy delay or drug reductions, while in 4 others chemotherapy was completed preliminarily. Nevertheless it did not affect patients' outcome overall survival in VOD group was 90%. CONCLUSIONS: Total 5% VOD frequency is similar to other reports. Infants and children receiving abdominal irradiation seem to be at special risk of VOD development.

Loss of heterozygosity of WT1 gene in the prognosis of sporadic Wilms' tumour in children.

The aim of this report was to evaluate the prognostic value of allele loss of the WT1 gene in children with sporadic Wilms' tumour. Allele loss of the WT1 gene was evaluated using microsatellite polymorphisms in the 3' untranslated region of WT1 in a radioactive PCR assay. The study comprised 66 children (30 girls and 36 boys), aged from 2 days to 13 years, treated for Wilms' tumour according to the SIOP-09 and PGGL scheme. We have used DNA isolated from the neoplastic versus normal kidney tissue from the paraffin embedded sections using microdissection procedure. Loss of heterozygosity (LOH) of the WT1 gene was found in 12 children (19.6%), 5 cases were non-informative. No significant correlation could be found between the LOH of WT1 gene and sex and age. Significantly more frequent occurrence of LOH in tumor in low stage of advancement and low degree of malignancy was found. However, no significant effect of LOH of WT1 gene was observed on frequency of recurrences, metastasis and deaths. Study of allele loss of the WT1 gene may be recommended in difficult cases as an additional factor useful for the diagnosis and in the assignment of the tumour to the appropriate risk group.