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V Reuter

Publications and source records attributed to V Reuter.

At least 19 recordsLinked to original sources
PubMed2006

Joint association of polymorphism of the FGFR4 gene and mutation TP53 gene with bladder cancer prognosis.

The impact of the fibroblast growth factor receptor 4 (FGFR4) Gly388Arg polymorphism on bladder cancer is unknown. We found no clear correlations between the FGFR4 genotype and risk of bladder cancer or pathological parameters. Neither the polymorphism nor TP53 mutation status was an independent predictor of prognosis, but they might act jointly on the disease-specific survival of patients.

Aged↗
PubMed2006

Long-term outcome among men with conservatively treated localised prostate cancer.

Optimal management of clinically localised prostate cancer presents unique challenges, because of its highly variable and often indolent natural history. There is an urgent need to predict more accurately its natural history, in order to avoid unnecessary treatment. Medical records of men diagnosed with clinically localised prostate cancer, in the UK, between 1990 and 1996 were reviewed to identify those who were conservatively treated, under age 76 years at the time of pathological diagnosis and had a baseline prostate-specific antigen (PSA) measurement. Diagnostic biopsy specimens were centrally reviewed to assign primary and secondary Gleason grades. The primary end point was death from prostate cancer and multivariate models were constructed to determine its best predictors. A total of 2333 eligible patients were identified. The most important prognostic factors were Gleason score and baseline PSA level. These factors were largely independent and together, contributed substantially more predictive power than either one alone. Clinical stage and extent of disease determined, either from needle biopsy or transurethral resection of the prostate (TURP) chips, provided some additional prognostic information. In conclusion, a model using Gleason score and PSA level identified three subgroups comprising 17, 50, and 33% of the cohort with a 10-year prostate cancer specific mortality of <10, 10-30, and >30%, respectively. This classification is a substantial improvement on previous ones using only Gleason score, but better markers are needed to predict survival more accurately in the intermediate group of patients.

Aged↗
PubMed2001

Histologic classification of penile carcinoma and its relation to outcome in 61 patients with primary resection.

A retrospective review of the clinical and pathologic features of 61 cases of penile squamous cell carcinoma (SCC), all treated by primary surgical resection at the Memorial Sloan Kettering Cancer Center during the period 1949-1992, was undertaken. Inguinal lymph node dissection material was evaluated in 40 cases. All carcinomas were of squamous cell type and were classified as follows: usual type, 36 cases (59%); papillary, not otherwise specified (NOS), 9 cases (15%), basaloid, 6 cases (10%); warty (condylomatous), 6 cases (10%); verrucous, 2 cases (3%), and sarcomatoid, 2 cases (3%). A high rate of nodal metastasis and poor survival were found for the basaloid and sarcomatoid neoplasms (5 of 7 patients with metastasis, 71%, and 5 of 8 dead of disease, 63%). Only 1 patient with a verruciform tumor (defined as a tumor of nonspecific papillary, warty, or verrucous type) had inguinal node metastasis and none died from penile cancer. An intermediate rate of metastasis and mortality (14 of 26, 54%, and 13 of 36, 36%, respectively) was found for typical SCC. Penile carcinomas are morphologically heterogeneous, and there is a correlation of histologic type and biologic behavior. This mandates accurate histologic subtyping by the pathologist.

Adult↗
PubMed2001

Cystectomy for bladder cancer: a contemporary series.

PURPOSE: To validate the current TNM staging system, we analyzed our contemporary experience with 300 cystectomies. MATERIALS AND METHODS: The pathological material and medical records of 300 patients treated with cystectomy were reviewed, and the new TNM classification was adopted. RESULTS: The median followup of patients with no evidence of disease was 65 months, and overall survival rate was 45% with a median survival of 50 months. In a Cox regression analysis only patient age, pT stage and neoadjuvant chemotherapy were significant factors for survival. The disease specific survival was 67% with a median survival of 94 months. In a multiple proportional hazards analysis only pT stage and previous chemotherapy were significant factors of disease specific survival. A significant difference was seen in the overall and disease specific survival between patients with organ confined and nonorgan confined tumors. We did not observe a difference in the survival rate among patients with pT4a to pT3 tumors. Significant differences were not seen in survival rates between sexes or among patients of different age groups. Transitional cell carcinoma was the predominant histological type, and no significant difference was found in patient outcome among the different histological subtypes. CONCLUSIONS: Bladder cancer can be categorized into organ confined and nonorgan confined tumors. This dichotomous grouping is better suited for evaluating adjuvant clinical trials. The pT stage of the bladder and prostate should be prospectively analyzed together to better define the clinical implications of prostatic involvement. In our opinion the histological subtypes do not affect outcome.

Adult↗
PubMed2001

A postoperative prognostic nomogram for renal cell carcinoma.

PURPOSE: Few published studies have combined prognostic factors to predict the likelihood of recurrence after surgery for renal cell carcinoma. We developed a nomogram for this purpose. MATERIALS AND METHODS: With Cox proportional hazards regression analysis, we modeled pathological data and disease followup for 601 patients with renal cell carcinoma who were treated with nephrectomy. Predictor variables were patient symptoms, including incidental, local or systemic, histology, including chromophobe, papillary or conventional, tumor size, and pathological stage. Treatment failure was recorded when there was either clinical evidence of disease recurrence or death from disease. Validation was performed with a statistical (bootstrapping) technique. RESULTS: Disease recurrence was noted in 66 of the 601 patients, and those in whom treatment was successful had a median and maximum followup of 40 and 123 months, respectively. The 5-year probability of freedom from failure for the patient cohort was 86% (95% confidence interval 82 to 89). With statistical validation, predictions by the nomogram appeared accurate and discriminating with an area under the receiver operating characteristic curve, that is a comparison of the predicted probability with the actual outcome of 0.74. CONCLUSIONS: A nomogram has been developed that can be used to predict the 5-year probability of treatment failure among patients with newly diagnosed renal cell carcinoma. The nomogram may be useful for patient counseling, clinical trial design and patient followup planning.

Carcinoma, Renal Cell↗
PubMed2001

Genetic alterations in tp53 in recurrent urothelial cancer: a longitudinal study.

PURPOSE: Because bladder cancer has a recurrence rate that can be as high as 90% at 2 years, we sought to clarify whether these metachronous tumors are polyclonal or monoclonal in origin. We have examined the genetic alterations of the TP53 gene in a cohort of patients with urothelial cancer who underwent multiple biopsies at different times and sites because of tumor recurrence and/or progression. We postulated that if tumor cells at different points in the natural history of the disease contain an identical mutation in the TP53 gene, this pattern could provide evidence for the monoclonality of the recurrent bladder tumors. EXPERIMENTAL DESIGN: Fifty-three biopsy specimens from 13 patients at different times and sites were selected for this study. Microdissection was used to ensure the purity of tumor cells. DNA extraction, PCR, and direct sequencing of exons 5 through 8 of the TP53 gene were conducted following protocols optimized in our laboratory. RESULTS: We found that specimens from seven patients carried tumor-specific TP53 mutations. The number of lesions in these patients ranged from two to seven, extending from 2 to 4 years. All of the seven patients displayed identical mutations in the different microdissected tumors. CONCLUSIONS: On the basis of these data, it appears that the recurrent bladder tumors originate from the same clone.

DNA Mutational Analysis↗
PubMed2000

Carcinoid tumor of the kidney. The use of somatostatin receptor scintigraphy in diagnosis and management.

Three patients were diagnosed with carcinoid tumors of the kidney. The diagnosis was rendered after biopsy with the assistance of immunohistochemical stains. In all three patients, a pentetreotide scan was helpful in staging. Metastatic disease that was not evident by computed tomography was found in one patient. All three patients are alive with stable or slowly progressive disease at 33, 36, and 40 months. Carcinoid tumors arising from the kidney are rare but must be considered in the differential diagnosis of a renal mass. Immunohistochemical staining is important in the diagnosis of these tumors and the pentetreotide scan contributes to accurate staging.

Journal Article↗
PubMed2000

Extensively necrotic cystic renal cell carcinoma: a clinicopathologic study with comparison to other cystic and necrotic renal cancers.

Renal cell carcinomas often show varying degrees of necrosis and cystic change. The prognostic importance of necrosis so extensive that only a few tumor cells can be identified is not clear. We gathered clinicopathologic and follow-up data on a group of eight such cases ("type I"). These patients were compared with two other groups of renal cell carcinomas: those with extensive necrosis (>50%), yet with readily identifiable tumor ("type II"), and cancers with extensive cystic change not resulting from necrosis, usually multiloculated ("type III"). The groups showed similar demographic characteristics, and within each group there was great variation in tumor size. Conventional (clear cell) histology was more common than papillary morphology in all groups. The type II neoplasms tended to be of higher nuclear grade and pathologic stage than the other groups. While one of six type I patients with follow up progressed 131 months after diagnosis, eight of 20 type II patients showed progression. None of the six type III patients with follow up progressed. We conclude that renal cell carcinomas showing extensive necrosis are capable of aggressive behavior, and patients with these lesions cannot be assured of cure following surgery. Pathologists must be aware of this entity and extensively sample any renal lesion showing extensive necrosis. The tumors showing a greater amount of viable neoplastic cells yet at least 50% necrosis had a higher rate of progression than did the type I patients. The lack of progression of any of the type III cases supports the idea that type III multiloculated cystic renal cell carcinomas may carry a distinctly better prognosis than other forms of renal cell carcinoma.

Adult↗
PubMed2000

Three-dimensional ultrasound analyses of the prostate.

Although conventional ultrasonography has proven to be clinically useful for depicting many types of cancerous lesions, it cannot distinguish reliably between cancerous and noncancerous tissue of the prostate. Therefore, conventional transrectal ultrasonography (TRUS) is used primarily for general evaluations of the gland and for guiding biopsies based on clearly imaged anatomic features such as the capsule, seminal vesicles, and urethra. Spectrum analysis extracts ultrasound signal parameters associated with biopsy-proven tissue types, and these parameters are then classified using neural network tools such as learning vector quantization, radial basis, and multilayer perceptron algorithms. Classification of cancerous and noncancerous prostate tissue using neural networks produces receiver operating characteristic (ROC) curves of 0.87 +/- 0.04 compared with 0.64 +/- 0.04 for conventional ultrasonography. To image the prostate using these methods, parameter values are computed at each pixel location, then translated into a score for the likelihood of cancer using a look-up table generated using the best classification algorithm. The score for cancer likelihood is expressed as a gray-scale or color value, and the resulting image may be useful to guide biopsies or therapy. Changes in parameter or score values over time potentially can be used to assess progression of disease or efficacy of therapy.

Adenocarcinoma↗
PubMed1999

Progress in Two-Dimensional and Three-Dimensional Ultrasonic Tissue-Type Imaging of the Prostate Based on Spectrum Analysis and Nonlinear Classifiers.

Spectrum analysis of radiofrequency (RF) ultrasonic echo signals often can sense tissue differences that are not visible on conventional ultrasonic images. Spectrum-analysis parameter values combined with other variables, such as serum prostate specific antigen (PSA) concentration, can be classified by neural networks to distinguish effectively between cancerous and noncancerous prostate tissues. Images based on neural network classification of spectral parameters and clinical variables can be advantageous for biopsy guidance, staging, and treatment planning and monitoring. A study based on 644 biopsies from 137 patients showed that these methods are significantly superior to B-mode image interpretation for differentiating cancerous from noncancerous prostate tissues. Using the histologic determination of tissue types as the gold standard, the area under the receiver-operator characteristic (ROC) curve for neural network classification based on spectrum analysis and PSA value for the 644 biopsies was 0.87 +/- 0.04, and the ROC curve are for a level-of-suspicion (LOS) assignment based on B-mode imaging was 0.64 +/- 0.04. Color-encoded and gray-scale images derived from neural network assignment of suspicion for cancer at each pixel location showed remarkable detail and suggested potential clinical value for biopsy guidance using real-time two-dimensional (2D) images and staging, treatment planning, and monitoring using three-dimensional (3D) images.

Journal Article↗
PubMed1998

Bilateral non-familial renal cell carcinoma.

BACKGROUND: Bilateral renal cell carcinoma (RCC) exists in hereditary forms (von Hippel-Lindau disease, hereditary papillary renal cell carcinoma, and hereditary clear cell renal carcinoma) associated with various chromosomal abnormalities, and non-hereditary, apparently sporadic forms. The focus of this study is the clinical description of the latter entity. METHODS: Synchronous and asynchronous bilateral RCC were identified from a prospective database of 698 consecutive patients undergoing operation for RCC between July 1989 and December 1997 at Memorial Sloan-Kettering Cancer Center. Non-familial RCC was defined as that occurring in those patients without a family or hereditary history of RCC. Patients' records were evaluated for presentation, surgical approach used, and pathology. Actuarial survival from the date of initial operative treatment until the date of last follow-up or death was determined using the Kaplan-Meier method. Comparisons between groups were made using the Mann-Whitney test. RESULTS: Thirty-three of 698 (4.7%) patients operated for RCC had bilateral disease. Four of the 33 (12.1%) patients had either VHL or documented hereditary RCC, and 29 of 33 (87.9%) had non-familial RCC. Of the 29 patients, histology was conventional (clear cell) in 17 patients, papillary in 5, oncocytoma in 3, and unclassified in 3. One patient had a conventional (clear cell) histology in the first nephrectomy specimen and chromophobe renal cell carcinoma in the second. Partial nephrectomy was used in 100% of patients. Median follow-up time was 52 months. Actuarial 5-year overall survival was 84.5%, and actuarial disease-specific survival was 93.3% at 5 years for the non-familial RCC patients. CONCLUSIONS: Non-familial bilateral RCC patients represent a distinct subpopulation of renal cancer patients with a good overall prognosis. Partial nephrectomy is an integral part of the surgical management. Although most bilateral tumors present synchronously, asynchronous lesions may occur many years after original nephrectomy, thus committing the patient to long-term follow-up.

Adult↗
PubMed1998

Interferon-gamma and monoclonal antibody 131I-labeled CC49: outcomes in patients with androgen-independent prostate cancer.

To assess the tumor targeting, safety, and efficacy of monoclonal antibody 131I-labeled CC49 in patients with androgen-independent prostate cancer, 16 patients received 75 mCi/m2 of the radiolabeled antibody after 7 days of IFN-gamma pretreatment. Sequential tumor biopsies in three patients showed a median 5-fold (range, 2-6-fold) increase in the proportion of cells staining positively for the TAG-72 antigen, whereas one showed a decrease in staining. Fourteen patients received 131I-labeled CC49, whereas 2 showed a disease-related decrease in performance status, precluding antibody treatment. The antibody localized to sites of metastatic androgen-independent prostate cancer in 86% (12 of 14; 95% confidence interval, 57-95%) of cases. Both osseous and extraosseous sites were visualized, and in six (42%) patients, more areas were visible when the radioimmunoconjugate was used than were apparent when conventional scanning techniques were used. The localization of the conjugate in the marrow cavity was usually a site not visualized by the radionuclide bone scan, in which the isotope localizes primarily to the tumor-bone interface. The dose-limiting toxicity was thrombocytopenia because five (36%) patients showed grade IV and seven (50%) showed grade III effects. In addition, six (42%) patients, four of whom were hospitalized, showed a flare in baseline pain, and four showed a decrease in pain. No patient showed a >50% decline in prostate-specific antigen, although radionuclide bone scans remained stable in four cases for a median of 4 months. The results are consistent with dosimetry estimates showing that the delivered dose to tumor was subtherapeutic and suggest that approaches that exclusively target the bone tumor interface or the marrow stroma may be unable to completely eradicate disease in the marrow cavity. For CC49, improving outcomes would require repetitive dosing, which was precluded by the rapid development of a human antimouse antibody response.

Aged↗
PubMed1997

Chromosome 16 in primary prostate cancer: a microsatellite analysis.

Cytogenetic and molecular genetic analyses of prostate cancer specimens have revealed nonrandom chromosomal deletions, affecting chromosomes 7q, 8p, 10q and 16q. Based on these data, we designed this study to further characterize the altered region(s) on chromosome 16 by evaluating 16 microsatellite markers on a population composed of 32 paired normal and primary prostatic tumor samples. The 16 microsatellites selected mapped to 11 distinct loci on 16q and 5 loci on 16p. No alterations were identified affecting 16p. However, 16 of 31 (51%) informative cases showed molecular alterations in at least one of the loci analyzed on 16q, consisting of 18 deletions and 11 bandshifts. Moreover, most of the deletions clustered at 6 microsatellite loci, mapping to the 16q22.1-23.1 region. Our results suggest that microsatellite alterations on the long arm of chromosome 16 are frequent events in prostate cancer, and that the 16q22.1-23.1 region might harbor a tumor suppressor gene involved in prostate cancer.

Adenocarcinoma↗
PubMed1997

Apoptosis induced in advanced CD8F1-murine mammary tumors by the combination of PALA, MMPR and 6AN precedes tumor regression and is preceded by ATP depletion.

The drug combination N-(phosphonacetyl)-L-aspartic acid (PALA), methylmercaptopurine riboside (MMPR) and 6-aminonicotinamide (6AN), referred to as PMA, induces regressions of advanced CD8F1 murine mammary carcinomas in vivo. We demonstrated that CD8F1 tumor regressions were preceded by the appearance of apoptotic bodies, as observed by microscopic examination of morphology and TUNEL endlabeling, and fragmentation of DNA into nucleosomal "ladder" patterns. These indications of apoptosis were present as early as 6 h after simultaneous administration of MMPR and 6AN and further increased by over fivefold during the next 3 to 6 h, then remained at 7 to 12.8% (0.6 to 2.4% in saline-treated controls) of the cell population for at least 24 h after MMPR + 6AN administration. The 5'-phosphate derivative of MMRP, MMPR-5P, which inhibits de novo purine biosynthesis, was present at a "steady-state" level, and significant (40%) depletion of ATP had occurred by 3 h and both of these events preceded the onset of apoptosis. In addition, MMPR-5P was retained in CD8F1 tumors at a high level over a prolonged period (> 96 h) even as tumors were undergoing regression. The prolonged presence of MMPR-5P was important for optimal chemotherapeutic effect, since treatment with iodotubercidin (IodoT), an inhibitor of MMPR/adenosine kinase, 6 h after MMPR+6AN administration prevented the prolonged accumulation of MMPR-5P and reversed the regression of CD8F1 tumors. In addition, compared to the PMA-treated group, there was a significant restoration of ATP levels after treatment with IodoT. In individual PMA-treated CD8F1 tumors the degree of ATP depletion was found to correlate with the degree of tumor shrinkage at 24 h, after tumors had sufficient time to respond to treatment. These results define the time-course of drug-induced apoptosis in CD8F1 tumors, show that ATP depletion occurs prior to apoptosis and demonstrate that prolonged retention of MMPR-5P is associated with optimal chemotherapy. Collectively, these results suggest that the depletion of ATP by PMA treatment may be a component of the biochemical apoptotic cascade in the CD8F1 tumor.

6-Aminonicotinamide↗
PubMed1997

Aberrant expression of cyclin D2 is an early event in human male germ cell tumorigenesis.

Human male germ cell tumors (GCTs) arise in the spermatocytic lineage, and subsets display embryonal-like differentiation. Virtually all GCTs exhibit multiple copies of the short arm of chromosome 12, even in carcinoma in situ/intratubular germ cell neoplasia, the earliest recognizable neoplastic lesion of germ cells. Among the candidate amplified genes mapped to 12p, expression of the cyclin D2 gene (CCND2) was deregulated in a panel of GCT cell lines, with the relative level of steady-state mRNA and protein inversely correlated with the pattern of differentiation characteristic of the cell line. GCT cell lines with a more differentiated phenotype, as indicated by an immunophenotypic analysis, displayed lower cyclin D2 expression with a concurrent increase in expression of the cell cycle inhibitor p21. In the GCT cell lines in which cyclin D2 was highly expressed, cyclin D2 was in complex with its expected catalytic partners (Cdk4 and Cdk6). Whereas no detectable cyclin D2 expression was evident in normal human germ cells, cyclin D2 was expressed in the abnormal germ cells of all carcinoma in situ/intratubular germ cell neoplasia lesions studied. In GCT specimens that displayed no evidence of differentiation (seminoma) or primitive differentiation (embryonal carcinoma), cyclin D2 expression was detected. However, in tumor specimens with certain patterns of differentiation (teratoma and yolk sac tumor), expression was down- or up-regulated depending on the pattern. Our data suggest that aberrant cyclin D2 expression is an early event in germ cell tumorigenesis.

Blotting, Northern↗
PubMed1997

Relative contribution of normal and neoplastic cells determines telomerase activity and telomere length in primary cancers of the prostate, colon, and sarcoma.

Telomerase and telomere length are increasingly investigated as potential diagnostic and prognostic markers in human tumors. Among other factors, telomerase and telomere length may be influenced by the degree of tumor cell content in tumor specimens. We studied telomerase activity and telomere length with concomitant integration of histopathological data to determine whether both were influenced by the amount of tumor cells. We measured telomerase in 153 specimens: in 51 solid tumor blocks; in 51 cryostat sections; and in 51 adjacent normal tissues from patients with sarcoma (n = 10) and colorectal (n = 11) and prostate cancer (n = 30) using the sensitive and rapid detection telomeric repeat amplification protocol assay. Telomere length was determined by telomere restriction fragment Southern blot analysis. From cryostat sections, tumor cell infiltration was assessed. Telomerase activity was detected in all colorectal tumors and sarcomas, as expected. In primary prostate cancer, however, telomerase activity was less frequently observed (14 of 30, 47%). Moreover, a decreased intensity compared to colon cancer and sarcoma was evident (P < 0.001). The median tumor cell infiltration was significantly higher in sarcoma (65%) and colon (30%) compared to prostate cancer (5%; P < 0.001). There was a positive correlation between tumor cell infiltration and telomerase activity (r = 0.89; P < 0.001). Telomere restriction fragments in tumors were shorter compared to the normal tissues with peak differences in colon, sarcoma, and prostate of 1.8, 2.8, and 1 kilobase pairs, respectively (P < 0.002). Our data suggest the presence of a positive correlation between the degree of tumor cell content in human solid tumors and the level of telomerase activity detected. We demonstrated that the amount of tumor cells also affects telomere restriction fragment analysis. Therefore, with the predominance of normal cells in tumor specimens, telomerase activity measured may not reflect the malignant phenotype, and telomere loss may be underestimated. This phenomenon was most evident in prostate cancer. Our results will have implications for the future when telomerase activity and telomere lengths may be used for early screening, diagnosis, and prognosis determinations and when telomerase inhibitors are applied to clinical practice.

Adenocarcinoma↗
PubMed1995

Chromosome 12 abnormalities in malignant ovarian germ cell tumors.

We analyzed 3 cases of malignant ovarian germ cell tumors (MOGCTs), comprising 1 dysgerminoma and 2 immature teratomas, by banded chromosome analysis and by in situ hybridization (ISH) using a chromosome 12p painting probe. We found evidence of 12p abnormalities in two of them. A possible common genetic pathway of origin of a subset of MOGCTs with testicular germ cell tumors (TGCTs) is discussed.

Aneuploidy↗