The survivin:fas ratio in pediatric renal tumors

BACKGROUND/PURPOSE: Apoptosis factors inducing or preventing cell death may govern the behavior of certain tumors. Fas is a pro-apoptotic receptor that induces cell death when bound by its ligand and is expressed at greater levels in pediatric renal tumors of good prognosis. Survivin is a novel inhibitor of apoptosis that is expressed in a cell cycle-dependent manner and is abundantly expressed in several tumors of unfavorable histology. This study evaluates the expression of survivin, as well as the prognostic value of the survivin:fas ratio in various types and stages of pediatric renal tumors. METHODS: Multiple apoptosis mRNA species were quantified by Rnase protection assay (RPA) in 32 pediatric renal tumors and adjacent normal kidney specimens before chemotherapy: Wilms' tumor (WT), n = 9; clear cell sarcoma (CCS), n = 4; rhabdoid tumor of the kidney (RTK), n = 5; mesoblastic nephroma (MN), n = 3 and normal kidney, n = 11. Western Blot and immunocytochemistry were used to confirm survivin protein expression in a selective specimen survey. Follow-up data were obtained on patient outcomes, and antiapoptotic to proapoptotic ratios were calculated and correlated with clinical recurrence of disease. RESULTS: Pediatric renal tumors express greater levels of both pro- and antiapoptotic factors than normal kidney. Survivin and fas appeared to be expressed differentially in the tumor specimens sampled. Five of 10 (50%) tumors that went on to recur expressed survivin, whereas survivin was present in only 2 of 11 (18%) nonrecurrent tumors. Conversely, only 2 of 10 (20%) tumors that recurred were fas positive, whereas 5 of 11 (45%) tumors that did not recur expressed fas. The mean survivin:fas ratio was significantly greater in the 10 tumors that went on to recur after treatment (4 RTK, 3 CCS, 3 WT), than in tumors not recurring (2.16+/-1.4 v 1.0+/-1.07; P =.01, Kruskal-Wallis test). The positive predictive value of tumor recurrence was 85.7% (CI: 42.1%, 99.6%) and the negative predictive value was 71.4% (CI: 41.9%, 91.6%) when a cutoff ratio of 1.6 was considered. CONCLUSIONS: The survivin:fas mRNA ratio is of prognostic value in its ability to predict recurrent disease in children undergoing treatment for pediatric renal tumors. In this series, a ratio of greater than 1.6 predicted recurrent disease with a high probability irrespective of clinical stage or pathologic type. Determining the survivin:fas ratio may guide treatment, follow-up and counseling of patients with pediatric renal tumors.     

Genetics of common progressive renal disease

Familial aggregation of common chronic kidney diseases provides a unique opportunity to investigate the susceptibility genetic and environmental factors. In the past decade, a wealth of new data has become available concerning the genetic susceptibility leading to numerous nephropathies. Knowledge of the genetic components allows better understanding of initiation and progression of these chronic kidney diseases. In addition, one can envision that identification of genetically susceptible individuals might lead to earlier diagnosis and potential reversal of the current epidemic of end-stage renal disease. The goal of the current discussion is to review various issues pertaining to the role of genetic factors in common chronic kidney diseases, as exemplified by two leading causes of end-stage renal diseases worldwide, nephropathy of type 2 diabetes and IgA nephropathy. The genetic and environmental interplay leading to the nephropathies is highlighted.     

Chemotherapy of pediatric brain-stem tumors

Forty-five children harboring brain-stem tumors were treated at the University of California, San Francisco, between 1969 and 1979. Pathological diagnoses were made in 19 patients. All patients received radiation therapy (RT). Thirteen patients received chemotherapy before, during, or immediately after RT. Twenty-four patients were treated with chemotherapy at the time of tumor progression, after initial treatment with RT alone. No statistically significant difference in time to tumor progression or survival was found for treatment with chemotherapy as an adjuvant to RT compared to treatment with RT alone followed by chemotherapy administered at the time of tumor progression. There were, however, more long-term survivors in the group that was first treated with chemotherapy at the time of tumor progression. There was no statistically significant correlation between survival and tumor pathology or location, although there were more long-term survivors among patients harboring low-grade gliomas and among patients with tumors confined to the midbrain. The authors documented the response of some brain-stem tumors to chemotherapy; however, cooperative controlled studies will be required to determine the optimum treatment for this disease.     

Genetics and biology of male germ cell tumors

The application of cytogenetic and molecular genetic techniques to the study of germ cell tumors has yielded many clues to the etiology and chemosensitivity of these tumors. With the advent of expression profiling and genome-scanning technologies, it may be possible to identify molecular markers of germ cell tumor outcome and molecular networks important in human development and chemotherapeutic response.     

Immunohistochemical analysis of hSNF5/INI1 distinguishes renal and extra-renal malignant rhabdoid tumors from other pediatric soft tissue tumors

Malignant rhabdoid tumor (MRT) is a highly aggressive neoplasm that occasionally demonstrates phenotypic overlap with other soft tissue malignancies. Molecular genetic analysis of MRT frequently demonstrates deletion or mutation of the hSNF5/INI1 gene, with corresponding reduced expression at the protein level. INI1 immunohistochemistry was performed to determine the utility of this method in assessing loss of INI1 expression in rhabdoid tumors. Twenty-seven MRTs with molecular analysis (19 renal, 8 extra-renal) were evaluated. Seventeen additional MRT (10 renal, 7 extra-renal) without INI1 molecular analysis were also analyzed. Loss of INI1 expression was observed in the tumor cells in all 44 cases. To determine the specificity of this assay, a variety of 45 pediatric soft tissue tumors, some of which occasionally display rhabdoid differentiation, were investigated. These included Ewing's sarcoma, Wilms' tumor, desmoplastic small round cell tumor, clear cell sarcoma, congenital mesoblastic nephroma, synovial sarcoma, undifferentiated sarcoma, rhabdomyosarcoma, and epithelioid sarcoma. Positive nuclear staining was found in all nonrhabdoid tumors examined. Of interest, synovial and epithelioid sarcomas exhibited variable and/or focal staining. INI1 antibody immunohistochemistry is useful in confirming the histologic diagnosis of renal or extra-renal rhabdoid tumor, especially for cases with indeterminate histologic features, equivocal immunophenotypic profiles, or uninformative molecular studies.     

Management of functioning pediatric adrenal tumors

AimThe aim of this study is to present our experience in the management of hormonally active adrenal tumors in children.Material and methodsWe did a retrospective chart review of all children with hormonally active adrenal tumors evaluated at the endocrinology clinic and operated at our institution between 1983 and 2019.ResultsThere were 75 patients included in the study, 58 with adrenocortical tumors (ACTs) and 17 with pheochromocytomas (PCCs). Within the group of patients with ACTs, there were 41 females and 17 males. The mean age was 58.3 (SD: 87.9; range: 9–211) months. The clinical manifestation of the tumor's hormonal activity was virilization in 37 cases, Cushing syndrome in 5, and mixed in 16. A positive family history was present in 11 patients (18.9%). The mean tumor size was 48.2 (SD: 22.4; range: 7–120) mm. The pathological diagnosis was adenoma in 42 cases, carcinoma in 15 cases, and macronodular hyperplasia in 1. Median follow-up was 192 (range: 50–290) months. Tumor recurrence occurred in 6 patients (10.3%), and there were three disease-related deaths (5%). Within the group of patients with PCCs, there were 11 males and 6 females. The mean age was 146.7 (SD: 71.2; range: 60–216) months. A positive family history was present in 7 patients (41.2%). The mean tumor size was 36.6 (SD: 16.7; range: 7–120) mm. The pheochromocytoma was classified as benign in 15 cases and as malignant in 2. During a median follow-up of 180 (range: 127–300) months, recurrence was observed in 6 cases (35.3%) and disease-related death in 1 case (5.9%).ConclusionsProper diagnosis and management at our referral center were associated with a high cure rate, even in cases of malignant tumors. Familial surveillance is highly recommended.Level of evidenceLevel IV.     

Neuroimaging of pediatric brain tumors.

This article covers techniques of imaging, posterior fossa tumors, and supratentorial tumors. Computed tomography and magnetic resonance imaging are commonly used in the diagnosis and evaluation of pediatric brain tumors. MR imaging is the primary imaging technique because it is more sensitive in the detection of small tumors, particularly those in the posterior fossa.     

Epidemiology of pediatric brain tumors.

Brain tumor research is unlike some other areas of cancer research, in which definite causes have been identified and prevention and treatment strategies may be developed. Primary brain tumors are heterogeneous with respect to several characteristics, and brain tumor research is hampered by this fact, as well as by the small numbers of cases, by the lack of a clearly established and consistently applied histopathologic classification scheme, and by geographical variations in diagnostic capabilities and mechanisms for case reporting. The current movement toward molecular epidemiology has resulted in several changes in the ways we will be able to investigate cancer etiologies in the future, and promises to be especially fruitful in the area of brain tumor research. The search is under way for biologic markers of risk exposures for various cancers, and for laboratory methods to identify those individuals who, because of their genetic qualities, are most likely to have brain tumors. There are probably multiple causes for brain tumors, incorporating both genetic and environmental pathways. Prior research has consistently identified few risk factors for brain tumors, such as ionizing radiation. Thus, collaborative efforts among clinicians, laboratory scientists, and epidemiologists, which make use of molecular epidemiologic methods, are perhaps of greater importance in this field than for cancers arising at other sites.     

Malignant renal tumors before one year of age. Experience of a North African pediatric surgery service

The malignant tumours of the kidney are not very frequent during the first year of life and pose diagnostic and therapeutic problems. The aim of this work is to make an analysis of the epidemiologic, clinical and anatomo-pathological characteristics of these tumours during the first year of life and a development on the therapeutic methods and their results. MATERIEL AND METHODS: This is a retrospective study of 8 observations of malignant tumours of the kidney whose first symptomatology appeared during the first year of life. RESULTS: The malignant tumours of the kidney observed before the one year age constituted 18% of the tumours of the kidney in the child. A female prevalence was noted with a sex-ratio of 0.6. The assessment of extension found cutaneous (one case), ganglionic (one case) and pulmonary (two cases) metastases. First chemotherapy was prescribed to five patients. The surgery consisted on a widened nephrectomy in seven cases and a tumorectomy for an infant presenting a nephroblastomatosis. The tumour corresponded to a nephroblastoma in seven cases and a rhabdoide tumour in the last case. Mortality was high (50%) caused by the toxicity of chemotherapy in three cases and an advanced stage of cancer in one case. CONCLUSION: Renal tumoral pathology occurring in infants less than one year of age poses true etiologic and therapeutic problems. The high frequency of the nephroblastoma and the absence of benign tumour in our series encourage us to evocate more often the malignant renal tumours and to practice per cutaneous biopsies in case of diagnostic doubt.