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M J Mihatsch

Publications and source records attributed to M J Mihatsch.

At least 19 recordsLinked to original sources
PubMed2001

Discovery of new DNA amplification loci in prostate cancer by comparative genomic hybridization.

BACKGROUND: DNA sequence amplifications are involved in the progression of many tumor types, and have also been found in advanced prostate cancer. The aim of this study was to detect new loci of DNA amplifications in prostate cancer. METHODS: Comparative genomic hybridization (CGH) was used for whole genome screening of DNA sequence copy number alterations in 27 advanced prostate cancers. RESULTS: The most prevalent changes were losses of 8p, 13q (52%, each), 6q (48%), 18q (37%), 5q (30%), 2q, 4q and 16q (26%, each), and gains of 8q (48%), Xq (40%), and Xp (26%). In addition, 16 high-level amplifications were found. These included Xq12 (five), 8q24 (two), and 11q13 (one) with known putative target genes (androgen receptor, MYC and Cyclin D1), and 1q21-25 (three), 10q22 (two), 17q23-24 (two), and 8q21 (one) where the target genes remain unknown. CONCLUSIONS: High-level amplifications at different chromosomal sites occur in advanced prostate cancer. The detection of amplified chromosomal regions may serve as a starting point to discover novel oncogenes involved in prostate cancer progression.

Aged↗
PubMed2001

CDKNA2A mutation analysis, protein expression, and deletion mapping of chromosome 9p in conventional clear-cell renal carcinomas: evidence for a second tumor suppressor gene proximal to CDKN2A.

Inactivation of tumor suppressor genes on chromosome 9p is considered a critical event in renal cell carcinoma pathogenesis. Alterations of CDKN2A on 9p21 have been reported in renal cancer cell lines, but their relevance for primary renal carcinomas is unclear. Loss of heterozygosity (LOH) was analyzed by using four polymorphic microsatellites at D9S970 (9p12-9p13), D9S171 (9p13), D9S1748 (9p21), and D9S156 (9p21) in 113 primary conventional clear-cell renal cell carcinomas (CRCCs). Allelic deletion was detected in 21 of 88 informative CRCCs (24%) with the highest rate of LOH being observed at D9S171 on 9p13 (20%). Chromosome 9p LOH was associated with short tumor-specific survival in stage pT3 RCC (P = 0.01). Fluorescence in situ hybridization analysis of 54 CRCCs revealed no homozygous CDKN2A deletions indicating that this mechanism of CDKN2A inactivation is rare in CRCC. Sequencing of 113 CRCCs showed that 13 tumors (12%) had a 24-bp deletion abrogating codons 4 through 11 of CDKN2A. Immunohistochemical CDKN2A expression was absent in normal renal tissue and was only detected in six of 382 CRCCs (1.5%) on a renal tumor microarray. These data suggest that CDKN2A alterations are present in a small subset of CRCCs and a second, yet unknown tumor suppressor gene proximal to the CDKN2A locus, may play a role in CRCC development.

Adenocarcinoma, Clear Cell↗
PubMed2001

A new cause of renal thrombotic microangiopathy: yttrium 90-DOTATOC internal radiotherapy.

The chelator somatostatin analogue dota-D-phe(1)-tyr(3)-octreotide (DOTATOC), which is stably labeled with the beta-emitting radioisotope yttrium 90 ((90)Y), is used as internal radiotherapy for the treatment of patients with advanced neuroendocrine tumors. We report 5 patients who developed chronic renal failure, caused in 3 patients by biopsy-proven thrombotic microangiopathy (TMA). Twenty-nine patients (14 men, 15 women) with normal renal function before therapy were treated with divided intravenous doses of (90)Y-DOTATOC approximately 6 weeks apart (mean normalized cumulative dose, 165.4 +/- 36.4 mCi/m(2)). Twenty-two of 29 patients were administered a normalized cumulative dose of 200 mCi/m(2) without side effects. Among the 7 patients (6 women, 1 man) administered a normalized cumulative dose greater than 200 mCi/m(2), 5 patients (4 women, 1 man) developed renal failure. Increasing serum creatinine levels were observed within 3 months after the last (90)Y-DOTATOC injection. The evolution was rapidly progressive in 3 patients, resulting in end-stage renal failure within 6 months. The remaining 2 patients developed chronic renal insufficiency (mean serum creatinine level, 300 micromol/L an average 16 months after the end of treatment). Renal biopsies performed in 3 patients showed typical signs of TMA involving glomeruli, arterioles, and small arteries. Patients treated with high-dose (90)Y-DOTATOC internal radiotherapy (cumulative dose > 200 mCi/m(2)) are at high risk to develop severe renal failure caused by TMA lesions. The histopathologic lesions are identical to those found after external radiotherapy, which suggests a causal relationship between (90)Y-DOTATOC and renal TMA.

Biopsy↗
PubMed2001

No complement receptor 1 stumps on podocytes in human glomerulopathies.

BACKGROUND: Type one complement receptor (CR1) is the only physiological inhibitor of complement on podocytes. CR1 is lost in different glomerulopathies, in particular in lupus nephritis, in which it has been suggested that CR1 is removed by proteolysis from the cell membrane. METHODS: To define whether proteolytic cleavage of CR1 on podocytes is a general phenomenon, we analyzed the expression of CR1 in different glomerulopathies using a monoclonal antibody against epitopes present on the extracellular portion of the molecule and a polyclonal antibody directed at the intracellular tail of CR1. The two antibodies were applied on sequential serial histologic sections of renal biopsy. RESULTS: In normal glomeruli, the two antibodies provided similar results, that is, strong staining of podocytes, and both were shown to recognize specifically CR1. Decreased expression of the extracellular portion of CR1 was observed in lupus nephritis (8/8), focal and segmental glomerulosclerosis (FSGS; 7/7), IgA nephritis (6/6), membranous glomerulonephritis (3/3), and minimal change disease (3/3). In each case, the decreased expression was accompanied by a simultaneous decrease of the expression of the intracellular tail of CR1 (Spearman's correlation coefficient rs = 0.951, P < 0.001). This observation was confirmed by analyzing focal glomerular lesions on sequential serial sections. CONCLUSION: These data indicate that there are no CR1 stumps on podocytes, even in lupus nephritis, and suggest that the CR1 loss on podocytes is not due to consumption but to decreased synthesis. A loss of CR1 synthesis might render podocytes highly sensitive to complement attack.

Antibodies, Monoclonal↗
PubMed2001

Coexistence of Fabry's disease and necrotizing and crescentic glomerulonephritis.

The coexistence of Fabry's disease, an X-linked hereditary disease, and other renal diseases, has rarely been described in the same patient. Combined Fabry's disease and pauci-immune necrotizing and crescentic glomerulonephritis (NCGN) is hitherto unreported. We present the clinical and pathologic data of two patients with combined Fabry's disease and NCGN. Both patients presented with fevers of unknown origin and progressive renal insufficiency, however, lacked any other pathognomic signs of Fabry's disease such as acroparesthesias, dyshidrosis, and cutaneous angiokeratomas. The possible pathogenic mechanisms and causal relationship between the two disease processes are discussed.

Adult↗
PubMed2000

Construction of evolutionary tree models for renal cell carcinoma from comparative genomic hybridization data.

Renal cell carcinoma is characterized by an accumulation of complex chromosomal alterations during tumor progression. Chromosome 3p deletions are known to occur early in the carcinogenesis, but the nature of subsequent events, their interrelationships, and their sequence is poorly understood, as one usually only obtains a single "view" of the dynamic process of tumor development in a particular cancer patient. To address this limitation, we used comparative genomic hybridization analysis in combination with a distance-based and a branching-tree method to search for tree models of the oncogenesis process of 116 conventional (clear cell) renal carcinomas. This provides a means to analyze and model cancer development processes based on a more dynamic model, including the presence of multiple pathways, as compared with the fixed linear model first proposed by Vogelstein et al. (N. Engl. J. Med., 319: 525-532, 1988) for colorectal cancer. The most common DNA losses involved 3p (61%), 4q (50%), 6q (40%), 9p (35%), 13q (37%), and Xq (21%). The most common gains were seen at chromosome 17p and 17q (20%). The tree model derived from the distance-based method is consistent with the established theory that -3p is an important early event in conventional (clear cell) renal cancer and supports the prediction made from the branching tree that -4q is another important early event. Both tree models suggest that there may be two groups of clear cell renal cancers: one characterized by -6q, +17q, and + 17p, and another by -9p, -13q, and -18q. Putative prognostic parameters were -9p and -13q. The distance-based tree clarifies that -8p (present in 12% of tumors) is a late event, largely independent of other events. In summary, tree modeling of comparative genomic hybridization data provided new information on the interrelationships of genetic changes in renal cancer and their possible order, as well as a clustering of these events. Using tree analysis, one can derive a more in-depth understanding of the renal cancer development process than is possible by simply focusing on the frequencies of genetic events in a given cancer type.

Carcinoma, Renal Cell↗
PubMed2000

Genetic changes in clinically organ-confined prostate cancer by comparative genomic hybridization.

OBJECTIVES: The genetic basis underlying prostate cancer development and progression is poorly understood. The primary aim of this study was to identify chromosomal regions important for progression in clinically localized prostate cancer removed by radical prostatectomy. METHODS: Comparative genomic hybridization was used for whole genome screening of DNA sequence copy number alterations in 28 pathologically organ-confined tumors (pT2) and 28 tumors with infiltration of the seminal vesicles (pT3b). RESULTS: Comparative genomic hybridization analysis showed on average 2.0 +/- 2.4 chromosomal alterations per tumor with more frequent losses (mean 1.3 +/- 1.8) than gains (mean 0.7 +/- 1.0). The percentage of tumors without alterations was higher in Stage pT2 (21%) than in Stage pT3b (50%). Losses of 8p (21%), 13q (21%), 5q (14%), 16q (14%), and 18q (13%) and gains of Xq (21%) and 8q (9%) were the most prevalent changes. Distinct regional alterations included minimal overlapping regions of loss at 5q13-q21, 6q14-q21, and 18q21-qter. There was only a small increase in the number of alterations from Stage pT2 to Stage pT3b (mean 1.6 +/- 2.3 versus 2.5 +/- 2.4). However, two individual alterations-gain of 8q and loss of 18q-were significantly more frequent in Stage pT3b than in Stage pT2 prostate cancer (P = 0.02 and P = 0.04, respectively), suggesting that genes in these regions may be important for prostate cancer progression. CONCLUSIONS: The detection of chromosome 8q gains and 18q losses and the identification of the corresponding target genes could become a molecular tool for better characterization of clinically localized prostate cancer.

Chromosome Aberrations↗
PubMed2000

Prognostic utility of the recently recommended histologic classification and revised TNM staging system of renal cell carcinoma: a Swiss experience with 588 tumors.

BACKGROUND: A new, internationally accepted histologic classification of renal cell carcinoma (RCC) and a new edition of the TNM staging system were introduced in 1997. In the latter, there was a dramatic change in the pT classification of organ-confined renal cancer in which the break point between category pT1 and pT2 was increased from 2.5 cm to 7 cm. METHODS: To study the significance of the new pT classification and the new recommendations for histologic classification, 588 nephrectomy specimens were reevaluated to define morphologic prognostic parameters in RCC. pT classification (TNM 1997), histologic subtype, histologic tumor grade, presence of necrosis, and sarcomatoid differentiation were assessed. RESULTS: The histopathologic review according to the new classification revealed 487 conventional (clear cell) (83%), 64 papillary (11%), 31 chromophobe (5%), and 6 collecting duct (1%) RCCs. Clinical follow-up was available for 470 RCCs. The new pT classification (1997) was strongly correlated with patient survival (P < 0.0001). Histologic grade, presence of necrosis, and sarcomatoid differentiation provided independent prognostic information on the clear cell subtype of renal cancer. Sarcomatoid differentiation, but not tumor necrosis, portended a dismal prognosis for patients with papillary RCC. Chromophobe RCC was associated with a significantly better prognosis than clear cell RCC (P = 0.05). Papillary RCC with scanty cytoplasm and small cells (type 1) behaved less aggressively than papillary tumors with eosinophilic cytoplasm and large cells (type 2; P < 0.001). CONCLUSIONS: Accurate histologic classification according to the new recommendations has implications because the prognostic importance of other histologic features that are of independent significance varies with tumor subtype. The data suggest that the new pT classification allows good separation of prognostic groups of patients with renal cancer.

Carcinoma, Renal Cell↗
PubMed2000

Testing for polyomavirus type BK DNA in plasma to identify renal-allograft recipients with viral nephropathy.

BACKGROUND: Reactivation of polyomavirus type BK (BK virus) is increasingly recognized as a cause of severe renal-allograft dysfunction. Currently, patients at risk for nephropathy due to infection with the BK virus are identified by the presence of cells containing viral inclusion bodies ("decoy cells") in the urine or by biopsy of allograft tissue. METHODS: In a retrospective analysis, we performed polymerase-chain-reaction assays for BK virus DNA in plasma samples from 9 renal-allograft recipients with BK virus nephropathy; 41 renal-allograft recipients who did not have signs of nephropathy, 16 of whom had decoy cells in the urine; and as immunocompromised controls, 17 patients who had human immunodeficiency virus type 1 (HIV-1) infection (stage C3 according to the classification of the Centers for Disease Control and Prevention) and who had not undergone transplantation. RESULTS: In all nine patients with BK virus nephropathy, BK virus DNA was detected in the plasma at the time of the initial histologic diagnosis (a mean [+/-SD] of 46+/-28 weeks after transplantation) and during the course of histologically diagnosed, persistent BK virus disease. In three of the six patients with nephropathy who were studied serially after transplantation, BK virus DNA was initially undetectable but was detected 16 to 33 weeks before nephropathy became clinically evident and was confirmed by biopsy. Tests for BK virus DNA in plasma became negative and the nephropathy resolved after the doses of immunosuppressive drugs were decreased in two patients and after removal of the renal allograft in three patients. BK virus DNA was found in the plasma of only 2 of the 41 renal-allograft recipients who had no signs of nephropathy and in none of the patients with HIV-1 infection. CONCLUSIONS: Testing for BK virus DNA in plasma from renal-allograft recipients with use of the polymerase chain reaction is a sensitive and specific method for identifying viral nephropathy.

BK Virus↗
PubMed2000

Allelic loss at the D9S171 locus on chromosome 9p13 is associated with progression of papillary renal cell carcinoma.

Papillary renal cell carcinomas (RCCs) have characteristic clinical and morphological features that separate them from the more common clear cell RCCs. The details of the molecular changes in papillary RCC progression are not well understood. In this study, four highly polymorphic microsatellite markers [D9S970 (9p12-9p13), D9S171 (9p13), D9S1748 (9p21) and D9S156 (9p21)] were used to determine the frequency and prognostic significance of 9p deletions in 37 papillary RCCs. Allelic deletions were detected in eight cases (22%). The highest rate of loss of heterozygosity (LOH) was observed in 6 of 29 informative patients (21%) at the D9S171 locus on 9p13. Only two patients displayed allelic loss at D9S1748, which resides in close proximity to p16(INK4). Two of 24 informative papillary RCCs (8%) showed LOH for D9S970. LOH at D9S171 (9p13) was associated with short patient survival (p=0.008), independently of tumour grade and stage. These data suggest a tumour suppressor gene centromeric to 9p21 that may contribute to papillary RCC progression.

Carcinoma, Papillary↗
PubMed2000

High-throughput tissue microarray analysis of cyclin E gene amplification and overexpression in urinary bladder cancer.

Studies by comparative genomic hybridization revealed that the 19q13 chromosomal region is frequently amplified in bladder cancer. The cyclin E gene (CCNE), coding for a regulatory subunit of cyclin-dependent kinase 2, has been mapped to 19q13. To investigate the role of cyclin E alterations in bladder cancer, a tissue microarray of 2,317 specimens from 1,842 bladder cancer patients was constructed and analyzed for CCNE amplification by fluorescence in situ hybridization and for cyclin-E protein overexpression by immunohistochemistry. Fluorescence in situ hybridization analysis showed amplification in only 30 of the 1,561 evaluable tumors (1.9%). Amplification was significantly associated with stage and grade (P: < 0.0005 each). Immunohistochemically detectable cyclin E expression was strong in 233 (12.4%), weak in 354 (18.9%), and negative in 1, 286 of the 1,873 interpretable tumors. The majority (62.1%) of CCNE-amplified tumors were strongly immunohistochemistry-positive (P: < 0.0001). The frequency of protein expression increased from stage pTa (22.2%) to pT1 (45.5%; P: < 0.0001) but then decreased for stage pT2-4 (29.4%; P: < 0.0001 for pT1 versus pT2-4). Low cyclin E expression was associated with poor overall survival in all patients (P: < 0.0001), but had no prognostic impact independent of stage. It is concluded that cyclin E overexpression is characteristic to a subset of bladder carcinomas, especially at the stage of early invasion. This analysis of the prognostic impact of CCNE gene amplification and protein expression in >1,500 arrayed bladder cancers was accomplished in a period of 2 weeks, illustrating how the tissue microarray technology remarkably facilitates the evaluation of the clinical relevance of molecular alterations in cancer.

Adult↗
PubMed2000

Clinical significance of interobserver differences in the staging and grading of superficial bladder cancer.

OBJECTIVE: To assess the reliability of the histological diagnosis of bladder cancer by assessing the interobserver variability of staging and grading in pTa/pT1 tumours and evaluating the clinical significance of discrepancies. MATERIALS AND METHODS: All sections from 301 superficial bladder carcinomas were reviewed by one pathologist. The prognostic relevance of grade and stage from both the initial and review diagnosis were determined in 128 patients for whom there was long-term follow-up information. RESULTS: There were significant interobserver differences in both the grading and staging of tumours. From a total of 235 tumours that were initially considered pT1, the reviewer classified 35% as pTa, 56% as pT1, 6% as pT1- (at least pT1), and 3% as pT2-4. In 39% of all biopsies there were interobserver differences in tumour grade. The prognostic significance of grade and stage differed between the initial pathology report and the reviewer's diagnosis. The reviewer's staging allowed a better estimate of the risk of subsequent tumour progression than the initial staging. Progression was significantly more common in 49 tumours in which the reviewer agreed with stage pT1 than in 29 tumours that were down-staged from pT1 to pTa (P = 0.0116). However, the initial tumour grade (P = 0.0386) but not the reviewer's grade (P = 0.2645) was significantly linked to progression. CONCLUSIONS: These results show that grading and staging by different pathologists have varying prognostic implications. If possible, biopsies from bladder tumours should be independently evaluated by two different pathologists before radical therapy is administered.

Adult↗
PubMed2000

Relationship between nonphenacetin combined analgesics and nephropathy: a review. Ad Hoc Committee of the International Study Group on Analgesics and Nephropathy.

BACKGROUND: The debate on the association between nonphenacetin-containing combined analgesics and renal disease has lasted for several years. METHOD: A peer review committee of scientists, selected jointly by the regulatory authorities of Germany, Switzerland, and Austria and the pharmaceutical industry was asked to critically review data on the relationship between nonphenacetin combined analgesics and nephropathy. RESULTS: The committee regarded epidemiologic evidence on nonphenacetin combined analgesics as inconclusive because of sparse information and substantial methodological problems. The committee also noted that a diagnosis of analgesic-associated nephropathy (AAN) in clinical practice usually depends on information about exposure before or in the early stages of the disease and is seldom accompanied by specific histologic evidence. The morphologic finding of papillary calcification can arise from other conditions and is not specific for AAN. For these reasons, the identification criteria for AAN should be reappraised with scientific methods to validate the diagnostic procedure. In the limited amount of experimental pharmacological data in humans and animals, the committee found no convincing evidence to confirm or refute the hypothesis that nonphenacetin combined analgesics are more nephrotoxic than single formulations. For caffeine taken with combined analgesics, the currently available information is not sufficient to postulate a harmful toxicological effect. CONCLUSION: The committee's two main conclusions were that sufficient evidence is absent to associate nonphenacetin combined analgesics with nephropathy and that new studies should be done to provide appropriate data for resolving the question.

Acetaminophen↗
PubMed2000

Metastatic patterns of prostate cancer: an autopsy study of 1,589 patients.

The prognosis of prostate cancer is mainly determined by the presence or absence of metastases. Nevertheless, the metastatic pathways in prostate cancer are not entirely understood. Among 19,316 routine autopsies performed from 1967 to 1995 on men older than 40 years of age, the reports from those 1,589 (8.2%) with prostate cancer were analyzed. Hematogeneous metastases were present in 35% of 1,589 patients with prostate cancer, with most frequent involvement being bone (90%), lung (46%), liver (25%), pleura (21%), and adrenals (13%). Several lines of evidence suggested the existence of a backward metastatic pathway through veins from the prostate to the spine in addition to classical hematogeneous tumor spread via the vena cava. First, there was an inverse relationship between spine and lung metastases, suggesting that metastasis to the spine is independent of lung metastasis. Second, the maximum frequency of spine involvement occurred in smaller tumors (4 to 6 cm) as compared with the maximum spread to lung (6 to 8 cm) and liver (>8 cm), suggesting that spine metastases precede lung and liver metastases in many prostate cancers. Third, there was a gradual decrease in spine involvement from the lumbar to the cervical level (97% v 38%), which is consistent with a subsequent upward metastatic spread along spinal veins after initial lumbar metastasis. The results of this study show that bone, lung, and liver are the most frequent sites of distant prostate cancer metastases. Besides the cava-type of metastasis through lung passage, there are strong arguments for the existence and clinical significance of a backward venous spread to the spine, which is likely to occur early in the metastatic process.

Adult↗
PubMed2000

BK-virus nephropathy in renal transplants-tubular necrosis, MHC-class II expression and rejection in a puzzling game.

We review BK-virus nephropathy (BKN) as a new complication that increasingly affects renal allografts and causes dysfunction. Since starting in 1996, we have seen 11 cases. Currently, the prevalence of BKN is 3% in our graft biopsies. The diagnosis can only be made histologically. The virus affects tubular epithelial cells that show characteristic intranuclear inclusion bodies. The major reason for impaired graft function and a possible way for viral particles to gain access to the blood via peritubular capillaries is necrosis of infected epithelial cells. BK-virus DNA in the plasma, which can be detected by PCR, is closely associated with nephropathy. BK-virus does not stimulate tubular MHC-class II expression as judged by immunofluorescence double labelling. The inflammatory response is inconsistent and the frequency of rejection episodes is not increased during disease. Clinical manifestation of viral nephropathy evolves in several stages. (i) Initial, asymptomatic and reversible activation of the virus, judged by the presence of inclusion bearing cells in the urine. (ii) High dose immunosuppressive drug regimens, often including tacrolimus. (iii) Tubular injury and viraemia as additional promoting conditions. BKN nephropathy was associated with graft loss in 45% of our patients. The remaining patients with persistent viral nephropathy showed renal dysfunction (serum creatinine levels on average 150% above baseline readings). Currently, no established antiviral therapy is available. We discuss attempts to lower immunosuppression as a means to control viral replication. We propose a diagnostic algorithm for screening and monitoring the disease.

Animals↗
PubMed2000

Calretinin as a marker for cardiac myxoma. Diagnostic and histogenetic considerations.

To study the usefulness of calretinin as an immunohistochemistry marker in the diagnosis of cardiac myxoma (CM) and the origin of myxoma cells, we examined 24 CMs and 9 fetal hearts with immunohistochemical methods on formalin-fixed paraffin-embedded tissues. We compared 24 CMs with 10 mural thrombi, 6 jaw myxomas, and 2 papillary fibroelastomas. Calretinin expression was identified in 100% of CMs and was negative in all cases of mural thrombi, jaw myxoma, and papillary fibroelastoma. Calretinin expression by the neoplastic cells in CM was strong and diffuse and had a cytoplasmic and a nuclear pattern. Calretinin expression in fetal hearts was found in autonomic ganglia cells in the subepicardial tissue of the atria and atrial appendages, along the interatrial and atrioventricular sulci, and in the atrial septum. Results clearly indicate that calretinin can be used as a marker for the diagnosis of CM and that it is a powerful tool for the differential diagnosis, most importantly with mural myxoid thrombi. Furthermore, the positive expression of calretinin by the autonomic neurons in the fetal heart and CM supports the concept that myxoma cells may originate from endocardial sensory nerve tissue.

Adolescent↗
PubMed1999

Chromosomal imbalances are associated with a high risk of progression in early invasive (pT1) urinary bladder cancer.

Many cytogenetic alterations are known to occur in urinary bladder cancer, but the significance of most of them is poorly understood. To define these chromosomal regions where clinically relevant genes may be located, a series of 54 pT1 urinary bladder carcinomas with clinical follow-up information (median, 52 months; range, 5-167 months) were examined by comparative genomic hybridization. The most frequent alterations included DNA sequence copy number gains at 1q22-24 (33%), 20q11.2-ter (33%), 8q22 and 17q21 (28% each), and 6p22 (15%) as well as deletions at Y (37%), 9p (31%), 9q22-33 and 11p14-ter (28% each), 11q23 (26%), 8p (24%), 13q31 (19%), 2q35-ter (17%), and 2q22-33 (11%). Whereas the histological grade was unrelated to prognosis (P = 0.9752), the risk of tumor progression was significantly associated with the number of deletions per tumor (P = 0.0014). Individual cytogenetic alterations that were linked to subsequent tumor progression included gains of 3p22-24 (P = 0.0112) and 5p (P = 0.0003) as well as losses of 4p11-15 (P = 0.0052), 5q15-23 (P = 0.0410), 6q22-23 (P = 0.0090), 10q24-26 (P = 0.0232), and 18q12-23 (P = 0.0005). Genes with a role for bladder cancer progression may be located at these regions.

Carcinoma↗