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Particularly in small brain biopsies, it might be difficult to distinguish reactive astrogliosis from low-grade or infiltration zones of high-grade astrocytomas. So far no immunohistochemical marker allows a reliable distinction. Recently, the over-expression of Wilms' tumor gene product WT1 was reported in astrocytic tumor cells. However, no sufficient data on WT1 expression in normal or reactive astrocytes are available. Therefore, we investigated WT1 expression in paraffin-embedded brain sections from 28 controls, 48 cases with astrogliosis of various etiology and 219 astrocytomas [World Health Organization (WHO) grades I–IV] by immunohistochemistry. In normal brains and in astrogliosis, expression of WT1 was restricted to endothelial cells. In astrocytomas, WT1-positive tumor cells were found in pilocytic astrocytomas (66.7% of cases), diffuse astrocytomas (52.7%) WHO grade II (52.7%), anaplastic astrocytomas (83.4%) and glioblastomas (98.1%). Overall, the majority of all astrocytic neoplasms (84.5%) expressed WT1. Establishing a cut-off value of 0% immunoreactive tumor cells served to recognize neoplastic astrocytes with 100% specificity and 68% sensitivity and was associated with positive and negative predictive values of 1 and 0.68, respectively. Therefore, WT1 expression in astrocytes indicates a neoplastic origin and might represent an important diagnostic tool to differentiate reactive from neoplastic astrocytes by immunohistochemistry. [ABSTRACT FROM AUTHOR]

Examines the roles of the forkhead/winged-helix transcription factor in vertebrate development. Isolation of a human hepatocyte nuclear factor/forkhead homolog (HFH)-4 cDNA; Implication of the unique pattern of HFH-4 expression during fetal development.

* Background.--Dysgenetic male pseudohermaphroditism (DMP) is a sexual differentiation disorder characterized by bilateral dysgenetic testes, persistent mullerian structures, and cryptorchidism in individuals with a 46,XY karyotype. However, the histologic criteria for the diagnosis of DMP are poorly established. Objective.--To determine gonadal histology in children with DMP. Patients and Methods.--Between 1996 and 1998, 13 patients with DMP were evaluated on our service. The clinical diagnosis of DMP was based on a 46,XY karyotype, sex ambiguity, high levels of follicle-stimulating hormone and low levels of antimullerian hormone, a decreased testosterone response to human chorionic gonadotropin stimulation without accumulation of testosterone precursors, and the presence of mullerian structures. Molecular sequencing the HMGbox region of the SRY gene did not reveal any mutations. Biopsies were performed for 22 of 26 gonads (patient age at the time of biopsy, 16 months to 10 years). Conventional microscopy was used to evaluate mean tubular diameter, tubular fertility index, and number of Sertoli cells per tubular profile. Results.--All 26 gonads were located outside of the labioscrotal folds. Their histologic features varied from only a reduction in tubular size to features of a streak gonad. Five of the 22 gonads grossly resembled a streak gonad. The mean tubular diameter was severely reduced ([is greater than] 30% reduction relative to the normal tubular diameter for the patient's age) in 4 gonads, markedly reduced (10%-30%) in 11 gonads, slightly reduced ([is less than] 10%) in one gonad, and normal in one gonad. The tubular fertililty index, expressed as the percentage of tubular profiles containing germ cells, was severely reduced ([is less than] 30% of normal values) in 9 gonads, markedly reduced (50%-30%) in 2 gonads, and normal in 6 gonads. The number of Sertoli cells per tubular profile was elevated in 16 gonads and normal in one gonad. Thin tubules surrounded by fibrous tissue were occasionally observed. Conclusion.--The histologic findings confirmed the clinical diagnosis of DMP in every patient in the present series. However, gonadal histology was variable, and careful morphometric evaluation may be necessary to establish the diagnosis. (Arch Pathol Lab Med. 2001;125:652-656), Dysgenetic male pseudohermaphroditism (DMP) is a sexual differentiation disorder diagnosed on the basis of morphologic features in patients with evidence of gonadal dysgenesis. Typically, patients have ambiguous genitalia, low testosterone [...]