The MDM‐2 (murine double minute 2) gene codes for a cellular protein that can bind to the p53 tumor suppressor gene product, thereby functioning as a negative regulator of p53. In order to define the role of the MDM‐2 gene in the pathogenesis of human acute myeloid leukemia, the expression and the sequence of the MDM‐2 gene were examined in samples of bone marrow and/or peripheral mononuclear cells of 38 patients by using immunostaining, polymerase chain reaction (PCR), single strand conformation polymorphism, and sequencing. Immunohistochemical staining detected a weak accumulation of the MDM‐2 protein in AML patients of FAB classification M4 and M5. RT‐PCR analysis revealed a heterogeneous expression pattern of MDM‐2 mRNA in AML samples of different FAB classification. An increased level of MDM‐2 mRNA expression was observed in 17 of 38 AML patients when compared to normal controls. No structural changes in a 488 bp region extending from nucleotide 890 to 1378 of the MDM‐2 cDNA were detected using RT‐SSCP and sequence analysis. In addition, heterogeneous expression of p53 transcripts was found with the highest p53 mRNA levels in AML M4 and M5. Interestingly, there seems to be a correlation between the relative ratios of p53 and MDM‐2 mRNA levels in AML M4 and M5: in 15 of 23 cases high p53 mRNA expression was directly associated with high levels of MDM‐2 transcripts. An exclusively intranuclear p53 immunostaining pattern was found in 10 of 16 (58%) AML FAB M4 and M5, whereas the remaining AML samples tested were negative for p53 (0/10). Using RT‐SSCP analysis and direct sequencing of the RT‐PCR amplification products of p53 exon 5–8, we observed that only 1 of 38 AML patients showed a point mutation in the p53 gene. This missense mutation occurred in the evolutionary highly conserved region of p53 at codon 255 (Ile to Phe). These data indicated that structural alterations of the p53 gene do not play an important role in the initiation and progression of AML. However, abrogation of p53 tumor suppressor function due to MDM‐2 overexpression may be an alternative molecular mechanism by which a subset of AMLs may escape from p53‐regulated growth control.

Fournier's gangrene is a well known often fatal fasziitis of the pelvic floor following ano-rectal, urologic and gynecologic infections. Although rarely it is described as a complication of operative anal procedures and predisposing factors such as diabetes, alcoholism, immune-defects and consumptive diseases. To our knowledge the described case of a lethal outcome after staplerhemorrhoidectomy is the first one reported in literature.

von Hippel-Lindau (VHL) disease is a pleiotropic disorder featuring a variety of malignant and benign tumors of the eye, central nervous system, kidney, and adrenal gland. Recently the VHL gene has been identified in the chromosomal region 3p25-26. Prognosis and successful management of VHL patients and their descendants depend on unambiguous diagnosis. Due to recurrent hemangioblastomas, a29-year-old patient without familial history of VHL disease was diagnosed to be at risk for the disease. Histopathological examination of a small renal mass identified a clear cell tumor with a G1 grading. Genetic characterization of the germline and of the renal tumor was performed. Polymerase chain reaction/single strand conformation polymorphism (PCR/SSCP) analysis with primers from the VHL gene identified a deletion of a single nucleotide in exon 2 in the patient's germline and in the tumor, but not in the DNA of his parents. This deletion therefore must be a de novo mutation. Comparative genome hybridization (CGH) and fluorescence in situ hybridization (FISH) analysis of the G1 tumor with differentially labelled yeast artifical chromosome (YAC) clones showed loss of 3p and of the 3p26 signals, respectively. In conclusion, we identified a de novo germline mutation in the VHL gene of a young patient and a somatic chromosome 3p loss at the homologous chromosome 3 in his renal tumor. Our results suggest a recessive mode of inactivation of the VHL gene, providing solid evidence for its tumor-suppressor gene characteristics. Our data show the diagnostic potential of genetic testing, especially in patients without VHL family history. Furthermore, the findings of homozygous inactivation of the VHL gene in a G1 tumor support the notion that the inactivation of the VHL gene is an early event in tumorigenesis of renal cell carcinoma.

Identity AliasCommon renal cell carcinoma; Conventional renal cell carcinoma; Non papillary renal cell carcinoma ClassificationClear cell renal cell carcinoma (cRCC) is a distinct subtype of renal cell carcinoma, possibly originating from mature renal tubular cells in the proximal tubule of the nehpron. Clinics and pathology EpidemiologyIt comprises 70-75% of cases.They show a male preponderance of 2:1.

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