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G Sauter

Publications and source records attributed to G Sauter.

At least 73 records · Page 4Linked to original sources
PubMed1999

Focal loss of CD44 variant protein expression is related to recurrence in superficial bladder carcinoma.

The majority of papillary transitional cell carcinomas of the bladder are localized tumors at initial diagnosis; identification of those developing recurrence and an aggressive behavior is important. CD44 variant proteins have been implicated in tumor progression and metastasis, and a correlation with adverse prognosis has been demonstrated in a variety of human tumors. Here, the usefulness of conventional CD44 protein immunohistochemistry as a prognostic parameter for recurrence of superficial transitional cell carcinomas was assessed in paraffin sections of 241 tumors with long-term follow-up. A highly significant association was found between focal loss of CD44v3 and -v6 immunostaining and short recurrence-free interval in noninvasive (pTa) transitional cell carcinomas (P = 0.005), but not in minimally invasive (pT1) carcinomas (P = 0.78). Our results indicate the value of conventional CD44 immunohistochemistry as an additional tool for identifying patients at high risk for recurrence of pTa transitional cell carcinomas. They also point to biological differences between noninvasive and minimally invasive transitional cell carcinomas of the bladder.

Carcinoma, Transitional Cell↗
PubMed1999

Polysomies but not Y chromosome losses have prognostic significance in pTa/pT1 urinary bladder cancer.

A disturbed cellular DNA content is of potential diagnostic and prognostic relevance in urinary bladder cancer. To evaluate the prognostic significance of individual chromosomal aberrations in superficial bladder cancer, specimens of 105 tumors (67 pTa, 38 pT1) were examined by fluorescence in situ hybridization (FISH). FISH allows quantitation of chromosomes on a cell by cell level. Centromere probes for the chromosomes Y, 1, and 17 were used. There was a strong association between polysomies of the chromosomes 1 (found in 46% of tumors) and 17 (40% of tumors, P < .0001). Polysomies (1 and 17) were significantly more frequent in pT1 than in pTa tumors (P < .0001 each). In pTa tumors, polysomies of both chromosomes were linked to a high risk of recurrences; polysomy 17 was associated with an increased risk of progression (P < .05 each). There was no significant association between polysomies and an unfavorable prognosis in pT1 carcinomas. Previous studies had suggested a prognostic role of Y losses in bladder cancer. However, Y losses were not linked to recurrences or tumor progression in pTa or pT1 tumors of 67 male patients. These data show that marked genetic differences exist between pTa and pT1 carcinomas. They also indicate that polysomies of different chromosomes may have prognostic relevance in pTa urinary bladder cancer.

Adult↗
PubMed1999

Patterns of metastasis in muscle-invasive bladder cancer (pT2-4): An autopsy study on 367 patients.

BACKGROUND: Metastatic status is an essential determinant of prognosis of patients with muscle-invasive bladder cancer treated by cystectomy, and preoperative metastases detection is crucial for treatment selection in these patients. To better understand the metastatic behavior of bladder tumors, autopsies of patients with muscle-invasive bladder carcinomas (pT2-4) were evaluated. METHODS: Protocols and histologic sections from autopsies of 367 patients with pT2-4 bladder cancer were reviewed. RESULTS: Metastases were found in 251 of 367 patients (68%). The most frequent sites of metastases were regional lymph nodes (90%), liver (47%), lung (45%), bone (32%), peritoneum (19%), pleura (16%), kidney (14%), adrenal gland (14%), and the intestine (13%). There was no difference in the frequency and location of metastases between 308 transitional cell carcinomas and 38 squamous cell carcinomas. The frequency of metastases increased with local tumor extension (patients with cystectomy: pT2, 36%; pT3a, 45%; pT3b, 69%; pT4, 79%; p < 0.0001). For all pT classifications, the frequency of metastases was slightly higher in patients treated by cystectomy (metastases in 45% of 29 pT2 and 89% of 28 pT4 tumors) than in patients without cystectomy (36% of pT2 and 79% of pT4 tumors). CONCLUSIONS: These results argue against relevant clinical differences between histologic tumor types. The high frequency of metastases in patients having undergone cystectomy indicates that metastasis often occurs before the time of diagnosis. This emphasizes the need for a better prediction of the metastatic capability of these tumors at the time of diagnosis.

Adult↗
PubMed1999

Tissue microarrays for gene amplification surveys in many different tumor types.

Gene amplifications are common in many different tumor types and may confer diagnostic, prognostic, or therapeutic information for patient management. Tedious experiments are often required to determine which tumor types have amplifications of a specific oncogene. To facilitate rapid screening for molecular alterations in many different malignancies, a tissue microarray consisting of samples from 17 different tumor types was generated. Altogether, 397 individual tumors were arrayed in a single paraffin block. To determine whether results from the literature can be reproduced on minute tissue samples (diameter, 0.6 mm), amplification of three extensively studied oncogenes (CCND1, CMYC, and ERBB2) was analyzed in three fluorescence in situ hybridization experiments from consecutive sections cut from the tissue microarray. Amplification of CCND1 was found in breast, lung, head and neck, and bladder cancer, as well as in melanoma. ERBB2 was amplified in bladder, breast, colon, stomach, testis, and lung cancer. CMYC was amplified in breast, colon, kidney, lung, ovary, bladder, head and neck, and endometrial cancer. These results confirm and even extend existing data in the literature on such amplifications. In summary, we applied three fluorescence in situ hybridization experiments to analyze amplifications of three oncogenes in three x 397 tumors within a week. This demonstrates the power of using minute arrayed tissue specimens for tumor screening.

Cyclin D1↗
PubMed1999

[Analysis of kidney tumors in trichloroethylene exposed workers by comparative genomic hybridization and DNA sequence analysis].

Environmental and occupational mutagens such as chemical agents are suspected to be involved in cancer development. However, a direct link between carcinogen exposure and genetic alterations has been established only in a few examples. Carcinogen involvement in renal cell carcinoma (RCC) was recently supported by reports of an increased frequency of RCC among workers exposed to Trichloroethylene (TRI) in Germany. The aim of this study was to evaluate the phenotype and the genotype of renal tumors in occupationally TRI-exposed patients. Sporadic RCCs from TRI nonexposed patients served as control. Normal and renal tumor tissues from 12 patients with occupational histories of solvents and TRI exposure were histologically analyzed. Comparative Genomic Hybridization (CGH) was used to screen for genomic alterations along all chromosomal arms. Tumor DNA was analyzed for mutations of the von Hippel-Lindau gene (VHL) on 3p25.5 by PCR and sequencing analyses. The histological analysis revealed 9 clear cell (75%), 2 papillary RCC (18%) and 1 oncocytoma (8%). In clear cell RCC, DNA losses were frequently observed on 3p (66%), 6q (56%), 9p and 4q (44% each) and 2q (33%). DNA gains were detected on 9q, 17 (33% each) and 5q (22%). DNA gains were identified on chromosome 7 and 17 in papillary RCC. Four VHL gene mutations were found in three clear cell RCC (33%) with 3p loss. Comparisons of these results with data obtained from sporadic RCC revealed no unique phenotype, genotype or mutation pattern in the VHL gene of renal tumors after TRI exposure. Therefore, further studies on the relevance of dose and exposure time for the nephrocarcinogenic effect of TRI are indicated.

Base Sequence↗
PubMed1999

[Identification of prognostic parameters for renal cell carcinoma by cDNA arrays and cell chips].

We report here an example of how the combined application of cDNA and tumor array can lead to the identification of a novel prognostic marker within a very short time. A cDNA array analysis was performed on 5184 cDNA clones on a filter to screen for genes with differential expression between the renal cancer cell line CRL-1933 and normal kidney tissue to identify genes with relevance in RCC. There were 89 differentially expressed genes in the cancer cell line, one of them coding for vimentin, a cytoplasmic intermediate filament. To determine the in vivo prevalence and prognostic significance of vimentin expression, a renal cancer tissue micro array containing 532 RCC specimen was constructed and vimentin expression was determined by immunohistochemistry. Vimentin expression was frequently seen in clear-cell (51%) and papillary RCC (61%), but rarely in chromophobe RCC (4%) and oncocytomas (12%). These results obtained from minute arrayed tumor samples match with previous findings on vimentin expression in renal tumors. Furthermore, vimentin expression was significantly associated with poor patient prognosis (p < 0.007) independently of grade and stage. These results suggest that tissue microarray analysis provides a rapid and powerful method to determine the prevalence and prognostic significance of novel candidate genes discovered to be involved in cancer development with large-scale cDNA expression arrays. The tissue array can be adapted as a routine tool in research laboratories for analyses of large tumor series at the DNA, RNA or protein level. With such a tool, cancer researchers can study vast numbers of tumor samples in a short time and can generate a wealth of data on the application of tumor markers.

Biomarkers, Tumor↗
PubMed1998

Carcinomas of the renal pelvis associated with smoking and phenacetin abuse: p53 mutations and polymorphism of carcinogen-metabolising enzymes.

Phenacetin abuse and smoking are established risk factors for transitional cell carcinomas of the urinary tract. In the present study, we analysed exposure and the clinical course of patients who underwent nephrectomy for transitional cell carcinoma of the renal pelvis. PCR-SSCP of archival, paraffin-embedded histological sections followed by direct DNA sequencing revealed that 29 of 89 (33%) renal pelvic carcinomas contained a p53 mutation. Double mutations were found in 4 tumours and triple mutations in 1 tumour. The incidence of p53 mutations was significantly higher in tumours with grades 3 and 4 than in those with grades 1 and 2 and higher in invasive than in non-invasive tumours. Furthermore, patients with carcinomas carrying a p53 mutation showed poorer survival than those without mutation. The type of p53 mutation in renal pelvic carcinomas was similar to that reported for bladder cancer, G:C-->A:T transition mutations being most frequent (45%, 33% of these at CpG sites), followed by G:C-->T:A and G:C-->C:G transversions. The incidence and type of p53 mutation did not differ significantly in patients with a history of phenacetin abuse, smoking or neither of these habits. This was also true for G:C-->T:A transversions (17.5% of mutations), which are considered typical of smoking-induced carcinomas at other sites, e.g., lung, oral cavity and oesophagus. Our results indicate that the frequency and pattern of p53 mutations are similar in transitional cell carcinomas of the bladder and the renal pelvis and do not reflect exposure to phenacetin and/or smoking. The frequency of genetic polymorphism in genes coding for carcinogen-metabolising enzymes (CYP1A1, NAT1, GSTT1 and GSTM1) was also independent of exposure. Although the sample size of our study does not allow definite conclusions, these data are compatible with chronic tissue damage as a causative factor in the evolution of urothelial carcinomas rather than pointing to a direct mutagenic effect of phenacetin and tobacco-specific carcinogens.

Aged↗
PubMed1998

Genetic alterations in primary bladder cancers and their metastases.

Bladder cancer progression is thought to be associated with sequential genetic events. To search for the specific genetic changes associated with the metastatic process, comparative genomic hybridization was performed on 22 primary tumors and 24 metastases (10 distant and 14 nodal metastases) from 17 patients with stage pT2-4 bladder cancer. There was a striking similarity between the genetic alterations present in the primary and metastatic tumor samples from the same patient. The mean number of genetic changes/tumor was 12.2 for primary tumors and 11.7 for metastases. There was a strong concordance in the specific aberrations present in each patient's primary and metastatic lesions (mean, 75%). Concordance was also high among multiple sites from an individual primary tumor (mean, 96%) and multiple metastases from the same patient (mean, 75%). There were no specific genetic changes overrepresented in the metastases compared with their primary tumors. Genetic alterations present in more than 40% of tumors included gains on 6p, 8q, 10q, and 17q and losses involving 8p, 10q, and Y. Two regions of high-level amplification were common: (a) 10q22.1-q23.1 (32.6%); and (b) 17q11-21.3 (23.9%; the locus of erbB-2). A summary statistic was developed to quantitate the degree of clonal relationships between biopsies from the same patient. These data support a model in which minimal clonal evolution occurs in the metastatic tumor cell population after the metastatic event. When comparing primary cancers from patients with and without metastases, however, several unique genetic changes were identified in those cancers with metastases, suggesting that these loci may harbor genes important to the metastatic process.

Aged↗
PubMed1998

Intratumoral heterogeneity of von Hippel-Lindau gene deletions in renal cell carcinoma detected by fluorescence in situ hybridization.

Although chromosome 3p deletions are considered an initial event in clear cell renal cell carcinoma (RCC), the reported prevalence of 3p deletions is highly variable. Because molecular analyses may be influenced by intratumoral heterogeneity, this study was performed to evaluate the genetic heterogeneity of the von Hippel-Lindau (VHL) gene (on 3p25.5) in RCC. Fifty-three clear cell and papillary RCCs were examined by dual-labeling fluorescence in situ hybridization with probes for the VHL gene and chromosome 3 centromere. The results were compared with histopathological phenotype, proliferative activity (Ki-67 labeling index) and 8p/17p deletions (both suggested to be linked to RCC progression). A clear-cut VHL deletion (in more than 40% of cells) was detectable in 69% of clear cell RCCs but was not detectable in nine papillary RCCs. A considerable genetic heterogeneity of VHL deletions was seen in clear cell RCCs including VHL-deleted subpopulations with different chromosome 3 counts within individual tumors as well as populations with and without VHL deletions. 8p22 and 17p13 deletions (each of which were detected in 18% of clear cell RCCs) were both linked to VHL deletions. However, 8p and 17p deletions were not associated with tumor grade, stage, or Ki-67 labeling index. The data indicate that some clear cell RCCs may develop independently of VHL alterations.

Carcinoma, Renal Cell↗
PubMed1998

EGF-r gene copy number changes in renal cell carcinoma detected by fluorescence in situ hybridization.

Expression of epidermal growth factor receptor (EGF-r) is a frequent event in renal cell carcinoma (RCC). To investigate the role of EGF-r gene copy number changes related to EGF-r overexpression, 50 RCC specimens were examined by fluorescence in situ hybridization (FISH) and immunohistochemistry. Dual-labelling FISH with a repetitive pericentromeric probe for chromosome 7 and a probe for the EGF-r gene (at 7p13) was performed to analyse the EGF-r copy number in relation to chromosome 7 copy number on a cell-by-cell basis. Polysomy 7 was frequent in all histological types of RCC. Chromosome 7 polysomy was found in 26 of 35 clear cell (74 per cent), nine of nine papillary, and three of three chromophobe RCCs. EGF-r gene copy number was closely associated with the chromosome 7 copy number on a cell-by-cell basis. No EGF-r gene amplifications were found. EGF-r positivity was found in 37 of 50 cases (74 per cent) by immunohistochemistry. EGF-r positivity was more common in clear cell (81 per cent) than in papillary tumours (40 per cent; P = 0.029). Neither chromosome 7 nor EGF-r gene copy number was associated with EGF-r expression, indicating that an increased gene dosage is not a mechanism of EGF-r overexpression in RCC.

Carcinoma, Renal Cell↗
PubMed1998

Pussycats and baby tigers: non-invasive (pTa) and minimally invasive (pT1) bladder carcinomas are not the same!

The histological distinction between non-invasive papillary transitional cell tumours (pTa) and minimally invasive bladder carcinomas (pT1) is critical because of an increasing tendency of urologists to perform early cystectomy for recurrent pT1 carcinomas. Nevertheless, the diagnosis of minimal stromal invasion is often difficult, resulting in considerable inter-observer variability. Recent studies have revealed marked genetic differences between the stages pTa and pT1. These data support models suggesting that pTa bladder tumours and pT1 carcinomas represent two entirely different tumour entities. pTa tumours appear to be genuinely benign and, independent of treatment, true progression is very rare. pT1 carcinomas are early stages of potentially highly malignant neoplasms requiring consequent surgical resection. It remains to be seen if molecular analysis will prove instrumental in better distinguishing pTa and pT1 bladder neoplasms and in identifying those individual tumours with a particularly high risk of progression.

Carcinoma↗
PubMed1998

Comparative genomic hybridization reveals frequent chromosome 13q and 4q losses in renal carcinomas with sarcomatoid transformation.

Renal cell carcinomas (RCCs) with sarcomatoid transformation show the most malignant behaviour of all renal carcinoma types. In this study, comparative genomic hybridization was used to screen for losses and gains of DNA sequences along all chromosome arms in 12 sarcomatoid (S) RCCs. On average, there were 8.6 aberrations per tumour. DNA sequence losses (5.2 +/- 4.4) were slightly more frequent than gains (3.4 +/- 2.6). DNA gains most often involved chromosomes 17 (33 per cent), 7, and 8q (25 per cent each). High-level co-amplification involving 11q22-23 and 7p21-22 in one SRCC was not present in adjacent non-sarcomatous tumour areas, raising the possibility of oncogene involvement at these loci for sarcomatoid transformation. DNA losses were most prevalent at 13q (75 per cent) and 4q (50 per cent), suggesting that inactivation of tumour suppressor genes at chromosomes 13q and 4q may be linked to sarcomatoid growth of RCC. It is concluded that SRCCs are genetically highly complex. Chromosomes 13q, 4q, 7p21-22, and 11q22-23 may carry genes with relevance for sarcomatoid growth in RCC.

Adult↗
PubMed1998

[Cytogenetic changes in prostatic carcinoma].

Development and progression of tumors is driven by a malfunction of specific genes. Although prostate cancer is one of the most frequent tumors, little is known about the genes involved. Cytogenetic and molecular examinations have shown that chromosomal deletions most frequently involve 7q, 8p, 10q, 13q, 16q, 17p and the Y chromosome. These loci may carry tumor suppressor genes with relevance for prostate cancer. DNA sequence copy number gains were most frequently observed at chromosomes 7, 8q, and 11q. These regions may carry currently unknown oncogenes. There is increasing evidence for a clinical relevance of genetic alterations. Polysomies of several chromosomes were shown to be associated with poor prognosis of prostate cancer patients. Androgen receptor amplification can be found in hormone-refractory carcinomas which may respond to total androgen blockage. For the future it is hoped that the identification of the genes involved in prostate cancer and the determination of their function could allow for significant improvements of treatment strategies for prostate cancer patients.

Biomarkers, Tumor↗
PubMed1998

Chromosomal imbalances in papillary renal cell carcinoma: genetic differences between histological subtypes.

Papillary renal-cell carcinoma (RCC) is a renal carcinoma variant with distinct gross, microscopic, and cytogenetic features. Recently, a type 1 (pale cytoplasm, small-cell) and a type 2 (eosinophilic cytoplasm, large-cell) subtype of papillary RCC have been described. Chromosomal alterations associated with these tumor types were examined in 25 papillary RCCs by comparative genomic hybridization. Relative copy number gains were frequently detected at chromosomes 7p (56%), 7q (44%), 12q (28%), 16q (32%), 17p (56%), 17q (76%), and 20q (32%). Chromosomal regions that were most often lost included 1p (24%), 4q (36%), 6q (40%), 9p (36%), 13q (36%), Xp (28%), Xq (36%), and Y (73%). There were clinical and genetic differences between the subtypes of papillary RCC. Type 2 tumors were of higher nuclear grade (P = 0.0012) and higher stage (P = 0.01) and had a worse prognosis (P = 0.03) than type 1 tumors. The number of DNA gains per tumor, especially gains of 7p and 17p, was significantly higher in type 1 than in type 2 tumors (P < 0.01). These data suggest the existence of two distinct morphological and genetic subgroups of papillary RCC. Losses of chromosome Xp were associated with short patient survival (P < 0.01). Despite the small number of cases, this finding suggests that a gene on chromosome Xp may contribute to papillary RCC progression.

Carcinoma, Papillary↗
PubMed1998

Patterns of chromosomal imbalances in advanced urinary bladder cancer detected by comparative genomic hybridization.

To identify genetic changes linked to bladder cancer progression we analyzed 90 invasive transitional cell carcinomas (37 pT1 and 53 pT2-4) by comparative genomic hybridization. The most frequent alterations included 1q+ (37%), 5p+ (24%), 6q- (19%), 8p-(29%), 8q+ (37%), 9p- (31%), 9q- (23%), 11p-(24%), 11q- (22%), 17q+ (29%), and 20q+ (28%). Interestingly, there were three groups of alterations that frequently occurred together (9p- and 11q13+/ 20q+ and 11q13+ or 17q+/1q+ and 3p+ or 11q-). These loci might carry genes that interact with each other in specific molecular pathways. There were remarkable genetic similarities between minimally and deeply invasive tumors of different histological grades, including a similar number of aberrations per tumor and an equal frequency of most individual alterations. However, deletions of 5q, 6q, and 15q and gains of 5p, 7p, and Xq were significantly more frequent in pT2-4 than in pT1 carcinomas. These loci may harbor genes that are important for bladder cancer progression.

Chromosome Aberrations↗
PubMed1998

Ki67 labeling index in core needle biopsies independently predicts tumor-specific survival in prostate cancer.

A better knowledge of the biological aggressiveness of individual tumors could facilitate the selection of treatment in prostate cancer patients. This study assesses the influence of histological and molecular features in core needle biopsy specimens of prostate cancer on tumor-specific survival. Formalin-fixed core needle biopsy specimens from 111 consecutive patients (mean follow-up, 5.0 years) were immunohistochemically examined for their proliferative activity (Ki67 labeling index [LI]) and expression of p53 and Bcl-2. Overexpression of p53 was found in 16% of the biopsy specimens and was mainly restricted to poorly differentiated tumors. Bcl-2 positivity was found in 20% of tumors. The median Ki67 LI was 7.5%. There was a strong relationship between Ki67 LI and Gleason grade, with a continuous increase in the proliferative activity from low-grade to high-grade tumors (P = .0006). Univariate tumor-specific survival analysis showed that high Gleason score (P = .0018), high percentage of biopsy tumor involvement (P = .0227), high Ki67 LI (P = .0007), and p53 positivity (P = .0024) were predictors of tumor-related death. A high Ki67 LI emerged as the only independent predictor of tumor-specific survival in multiparametric analysis. These results indicate that core needle biopsy specimens of the prostate not only are useful for diagnosis of malignancy but also can provide valuable prognostic information. Immunohistochemical examinations of molecular features may be a helpful adjunct for a better pretherapeutic assessment of prostate cancer aggressiveness and therefore contribute to an improved initial patient management.

Aged↗
PubMed1998

Tissue microarrays for high-throughput molecular profiling of tumor specimens.

Many genes and signalling pathways controlling cell proliferation, death and differentiation, as well as genomic integrity, are involved in cancer development. New techniques, such as serial analysis of gene expression and cDNA microarrays, have enabled measurement of the expression of thousands of genes in a single experiment, revealing many new, potentially important cancer genes. These genome screening tools can comprehensively survey one tumor at a time; however, analysis of hundreds of specimens from patients in different stages of disease is needed to establish the diagnostic, prognostic and therapeutic importance of each of the emerging cancer gene candidates. Here we have developed an array-based high-throughput technique that facilitates gene expression and copy number surveys of very large numbers of tumors. As many as 1000 cylindrical tissue biopsies from individual tumors can be distributed in a single tumor tissue microarray. Sections of the microarray provide targets for parallel in situ detection of DNA, RNA and protein targets in each specimen on the array, and consecutive sections allow the rapid analysis of hundreds of molecular markers in the same set of specimens. Our detection of six gene amplifications as well as p53 and estrogen receptor expression in breast cancer demonstrates the power of this technique for defining new subgroups of tumors.

Animals↗