Prospective analysis of circulating endostatin levels in patients with renal cell carcinoma.

Background: The aim of the current study was to assess circulating levels of endogenous endostatin in patients with renal carcinoma and to determine the relationship of these levels to circulating levels of vascular endothelial growth factor (VEGF) and prognosis.

Methods: The authors prospectively studied 66 patients (48 male, 18 female; mean age, 50 years) undergoing nephrectomy for renal carcinoma on clinical trials at the National Cancer Institute. Metastases were present in 51 of 66 patients (77%) at the time of nephrectomy.

Mutations in a novel gene lead to kidney tumors, lung wall defects, and benign tumors of the hair follicle in patients with the Birt-Hogg-Dubé syndrome.

Birt-Hogg-Dubé (BHD) syndrome is a rare inherited genodermatosis characterized by hair follicle hamartomas, kidney tumors, and spontaneous pneumothorax. Recombination mapping in BHD families delineated the susceptibility locus to 700 kb on chromosome 17p11.2.

Pheochromocytoma in von hippel-lindau disease: distinct histopathologic phenotype compared to pheochromocytoma in multiple endocrine neoplasia type 2.

Pheochromocytomas are rare neuroendocrine tumors that arise from chromaffin tissue. In a small subset of patients, pheochromocytomas occur as a manifestation of von Hippel- Lindau (VHL) disease. The histology of VHL-associated pheochromocytomas has not been reported in detail.

The contribution of VHL substrate binding and HIF1-alpha to the phenotype of VHL loss in renal cell carcinoma.

Clear-cell renal carcinoma is associated with inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene. VHL is the substrate recognition subunit of an E3 ligase, known to target the alpha subunits of the HIF heterodimeric transcription factor for ubiquitin-mediated degradation under normoxic conditions. We demonstrate that competitive inhibition of the VHL substrate recognition site with a peptide derived from the oxygen degradation domain of HIF1alpha recapitulates the tumorigenic phenotype of VHL-deficient tumor cells.

Partial adrenalectomy in patients with multiple adrenal tumors.

Most adrenal tumors are found incidentally and appear as small solitary nodules on abdominal imaging. Occasionally, work-up demonstrates multifocal or bilateral adrenal tumors. Certain patients are predisposed to multiple lesions, such as those with hereditary forms of pheochromocytoma as seen in von Hippel-Lindau disease, multiple endocrine neoplasia type II, and von Recklinghausen's disease.

The RASSF1A tumor suppressor gene is inactivated in prostate tumors and suppresses growth of prostate carcinoma cells.

We analyzed expression status of the recently identified tumor suppressor geneRASSF1A in primary prostate carcinomas and in prostate cell lines. We found complete methylation of the RASSF1A promoter in 63% of primary microdissected prostate carcinomas (7 of 11 samples). The remaining 4 samples (37%) were partially methylated, possibly because of contamination with normal cells.

VHL-mediated hypoxia regulation of cyclin D1 in renal carcinoma cells.

Renal cell carcinoma is associated with mutation of the von Hippel-Lindau (VHL) tumor suppressor gene. Cell lines derived from these tumors cannot exit the cell cycle when deprived of growth factors, and the ability to exit the cell cycle can be restored by the reintroduction of wild-type protein VHL (pVHL). Here, we report that cyclin D1 is overexpressed and remains inappropriately high in during contact inhibition in pVHL-deficient cell lines.

Specimen morcellation after laparoscopic radical nephrectomy: confirmation of histologic diagnosis using needle biopsy.

Background And Purpose: Laparoscopic radical nephrectomy (LRN) is being increasingly offered for the management of renal-cell carcinoma (RCC). Specimen removal may be performed through a small or hand-port incision or by specimen morcellation. Limited studies exist addressing the accuracy of histopathologic diagnosis in morcellated renal tumors.

Risk of renal and colonic neoplasms and spontaneous pneumothorax in the Birt-Hogg-Dubé syndrome.

The Birt-Hogg-Dubé syndrome, a genodermatosis characterized by benign tumors of the hair follicle, has been associated with renal and colonic neoplasms and spontaneous pneumothorax, but the risk of developing these disorders is unknown. We identified risk factors for renal tumors and spontaneous pneumothorax in 98 patients affected with the Birt-Hogg-Dubé syndrome, in 13 Birt-Hogg-Dubé haplotype carriers, and in 112 unaffected family members. Development of renal tumors was strongly associated with the Birt-Hogg-Dubé syndrome and age.

Biochemical diagnosis of pheochromocytoma: which test is best?

Context: Diagnosis of pheochromocytoma depends on biochemical evidence of catecholamine production by the tumor. However, the best test to establish the diagnosis has not been determined.

Objective: To determine the biochemical test or combination of tests that provides the best method for diagnosis of pheochromocytoma.

Serial analysis of gene expression in renal carcinoma cells reveals VHL-dependent sensitivity to TNFalpha cytotoxicity.

We have used serial analysis of gene expression (SAGE) to investigate the influence of the von Hippel-Lindau (VHL) gene on global gene expression profiles. SAGE libraries were prepared from renal cell carcinoma (RCC) lines that either lack (parental) or express wild-type VHL (wtVHL). Comparison of these libraries revealed some differentially expressed genes (Glut-1, for example) that were known to be influenced by VHL, but the majority of genes had not previously been reported to be affected by the cell's VHL status.

Evaluation of non-formalin tissue fixation for molecular profiling studies.

Using a general strategy for evaluating clinical tissue specimens, we found that 70% ethanol fixation and paraffin embedding is a useful method for molecular profiling studies. Human prostate and kidney were used as test tissues. The protein content of the samples was analyzed by one-dimensional gel electrophoresis, immunoblot, two-dimensional gel electrophoresis, and layered expression scanning.

Proteomic analysis of human prostate cancer.

Proteomics is a promising approach in the identification of proteins and biochemical pathways involved in tumorigenesis. In an effort to discover such proteins and pathways that are deregulated in prostate tumorigenesis, cellular proteomes of matched normal prostate epithelial cells and high-grade prostate cancer cells were analyzed by tissue microdissection, two-dimensional electrophoresis, and mass spectrometry. Forty protein alterations were detected in the tumors; however, the majority of these changes were not shared among the 12 neoplasms.

Determination of a minimal deletion interval on chromosome band 8p21 in sporadic prostate cancer.

Loss of the short arm of chromosome 8 is a common event in prostatic neoplasms. Previous studies indicate that there may be up to three separate tumor suppressor genes on chromosome arm 8p, based on patterns of allelic loss. The responsible gene or genes have yet to be identified.

Intentional resection of the diaphragm during cytoreductive laparoscopic radical nephrectomy.

Purpose: Laparoscopic radical nephrectomy is being performed more commonly. To our knowledge intentional resection of the diaphragm during laparoscopic radical nephrectomy for large renal tumors has not yet been described. We detail the laparoscopic management of diaphragmatic resection.

Percutaneous radio frequency ablation of small renal tumors: initial results.

Purpose: Thermal tissue ablation with radio frequency energy is an experimental treatment of renal tumor. We report early results of an ongoing trial of percutaneous radio frequency ablation for small renal tumors.

Materials And Methods: Patients with percutaneously accessible renal tumors were evaluated for radio frequency ablation.

The consequences of chromosomal aneuploidy on gene expression profiles in a cell line model for prostate carcinogenesis.

Here we report the genetic characterization of immortalized prostate epithelial cells before and after conversion to tumorigenicity using molecular cytogenetics and microarray technology. We were particularly interested to analyze the consequences of acquired chromosomal aneuploidies with respect to modifications of gene expression profiles. Compared with nontumorigenic but immortalized prostate epithelium, prostate tumor cell lines showed high levels of chromosomal rearrangements that led to gains of 1p, 5, 11q, 12p, 16q, and 20q and losses of 1pter, 11p, 17, 20p, 21, 22, and Y.

Comorbid genetic diseases, von Hippel-Lindau disease and spinocerebellar ataxia type 2, confounding the diagnosis of cerebellar dysfunction in an adolescent.

The authors report a 15-year-old female who presented with difficulties in ambulation as well as difficulties with balance and penmanship. She had a known genetic risk of von Hippel-Lindau (VHL; MIM 193300) disease, with a unique VHL mutation, but had no tumors of the brain or spine to explain her symptoms. Laboratory analysis of peripheral blood lymphocytes was targeted at genetic loci associated with ataxic disorders.

Retroperitoneoscopic-guided radiofrequency ablation of renal tumors.

Objective: Minimally invasive approaches to the management of renal tumors are being studied intensively in urology. Herein, we describe the use of multiple organ-sparing techniques for the management of tumors in a patient with von Hippel Lindau disease (VHL).

Materials And Methods: A 42 year-old woman with VHL underwent a right partial adrenalectomy and a left renal radiofrequency ablation (RFA) of two renal tumors.

Birt-Hogg-Dubé syndrome, a genodermatosis associated with spontaneous pneumothorax and kidney neoplasia, maps to chromosome 17p11.2.

Birt-Hogg-Dubé syndrome (BHD), an inherited autosomal genodermatosis characterized by benign tumors of the hair follicle, has been associated with renal neoplasia, lung cysts, and spontaneous pneumothorax. To identify the BHD locus, we recruited families with cutaneous lesions and associated phenotypic features of the BHD syndrome. We performed a genomewide scan in one large kindred with BHD and, by linkage analysis, localized the gene locus to the pericentromeric region of chromosome 17p, with a LOD score of 4.

The genetic basis of renal epithelial tumors: advances in research and its impact on prognosis and therapy.

The genetics of renal cell carcinoma continues to elucidate the pathways of kidney tumorigenesis. The relationship between the VHL gene and clear cell carcinoma, MET and papillary carcinoma, and the families of genes that they regulate, continues to be unraveled. New hereditary kidney cancer syndromes, like familial oncocytoma and the Birt-Hogg-Dubé syndrome, have been identified and the search for the genes that cause them is under way.

A randomized phase II trial of thalidomide, an angiogenesis inhibitor, in patients with androgen-independent prostate cancer.

Purpose: Thalidomide is a potent teratogen that causes dysmelia in humans. Recently, in vitro data suggested that it inhibits angiogenesis. Prostate cancer is dependent on the recruitment of new blood vessels to grow and metastasize.

Lack of retroperitoneal lymphadenopathy predicts survival of patients with metastatic renal cell carcinoma.

Purpose: Patients with metastatic renal cell carcinoma have a reported 5-year survival of 0% to 20%. The ability to predict which patients would benefit from nephrectomy and interleukin-2 (IL-2) therapy before any treatment is initiated would be useful for maximizing the advantage of therapy and improving the quality of life.

Materials And Methods: A retrospective analysis of the x-rays and charts of patients treated at the National Institutes of Health Surgery Branch between 1985 and 1996, who presented with metastatic renal cancer beyond the locoregional area and the primary tumor in place, was performed.

Pheochromocytomas in von Hippel-Lindau syndrome and multiple endocrine neoplasia type 2 display distinct biochemical and clinical phenotypes.

This study examined the mechanisms linking different biochemical and clinical phenotypes of pheochromocytoma in multiple endocrine neoplasia type 2 (MEN 2) and von Hippel-Lindau (VHL) syndrome to underlying differences in the expression of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis, and of phenylethanolamine N-methyltransferase (PNMT), the enzyme that converts norepinephrine to epinephrine. Signs and symptoms of pheochromocytoma, plasma catecholamines and metanephrines, and tumor cell neurochemistry and expression of TH and PNMT were examined in 19 MEN 2 patients and 30 VHL patients with adrenal pheochromocytomas. MEN 2 patients were more symptomatic and had a higher incidence of hypertension (mainly paroxysmal) and higher plasma concentrations of metanephrines, but paradoxically lower total plasma concentrations of catecholamines, than VHL patients.