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1.
In 72 patients with urothelial carcinoma of the renal pelvis or ureter the ploidy, deoxyribonucleic acid (DNA) heterogeneity and counts of cell cycle phases in the tumor were analyzed by means of single cell DNA cytophotometry with the intention of finding new prognostic factors in addition to those already known (stage and grade). Followup ranged from 1 to 8 years. The results of the DNA analyses were related to the tumor categories, histopathological grading of the tumors and clinical course. Malignancy grade 1 tumors showed DNA frequency peaks in the diploid range, while tumors assessed as malignancy grade 2 showed heterogeneous DNA distribution patterns. Malignancy grade 3 tumors exhibited 71% aneuploid and 29% tetraploid DNA values. The proliferation rate of the tumor cells was statistically significantly higher in malignancy grades 2 and 3 than in malignancy grade 1. The prognosis for grade 1 tumors is good, whereas it is unfavorable in the case of grade 3 tumors. For these 2 groups (patients with grades 1 and 3 tumors) DNA ploidy affords no additional prognostic information. Grade 2 tumors, on the other hand, are heterogeneous in respect to DNA ploidy although they exhibit the same histomorphological degree of differentiation. These tumors can be subclassified as aneuploid (biologically aggressive) and diploid or tetraploid (biologically less aggressive) tumors. There was also a positive correlation between T category and DNA ploidy. The cell lines were aneuploid in 38% of the patients with stage T1 tumors, 56% with stage T2 tumors and almost 85% with stage T3, N+ tumors. A significant correlation was found between the results of DNA cytophotometry and the clinical course of the disease. Patients with diploid tumor cell nuclei had no metastases and no local tumor progression for up to 8 years, whereas patients with aneuploid tumor cell nuclei suffered metastasis and local tumor progression within 24 to 36 months. The patients died of the tumor 36 months after primary diagnosis on the average. The determination of DNA ploidy, tumor heterogeneity and tumor cell proliferation by means of DNA cytophotometry affords valuable clues as to prognosis.  相似文献   

2.
Flow cytometry analysis was performed on 30 primary male urethral squamous cell carcinoma specimens. Nuclei were extracted from paraffin-embedded archival material and isolated nuclei were stained with propidium iodide. Bulbomembranous urethral tumors had a higher incidence of abnormal deoxyribonucleic acid ploidy patterns than penile urethral tumors (69 and 29 per cent, respectively). Of the tumors exhibiting a deoxyribonucleic acid diploid pattern and an abnormal (deoxyribonucleic acid tetraploid or aneuploid) histogram 18 and 93 per cent, respectively, showed tumor progression (p less than 0.001). None (0 per cent) of the low grade (grade 1 or 2) tumors with a deoxyribonucleic acid diploid pattern developed local recurrence or distant metastases, whereas 90 per cent of the low grade tumors with an abnormal deoxyribonucleic acid pattern progressed (p less than 0.002). Patients with tumors exhibiting deoxyribonucleic acid diploid ploidy had 5 and 10-year rates free of disease of 85 per cent. In contrast, patients with tumors with abnormal deoxyribonucleic acid ploidy patterns had 5 and 10-year rates of 20 and 0 per cent, respectively (p less than 0.001). Determination of deoxyribonucleic acid ploidy pattern by flow cytometry provides important prognostic information for male patients with primary squamous cell carcinoma of the urethra.  相似文献   

3.
Nuclear deoxyribonucleic acid ploidy was determined in 206 samples of well differentiated clear cell renal carcinoma via a previously described technique on paraffin-embedded archival material. Grade 2 tumors had a higher incidence of abnormal deoxyribonucleic acid patterns than grade 1 tumors. Of stage 1 well differentiated clear cell renal tumors 60 per cent had a normal deoxyribonucleic acid histogram pattern, whereas 67 per cent of higher stage tumors had an abnormal pattern. The existence of abnormal nuclear deoxyribonucleic acid histogram patterns in the primary tumor tissue had a significant correlation with subsequent development of metastatic disease, independent of tumor grade and stage. The 10-year actuarial survival rate was 62 per cent for patients with normal deoxyribonucleic acid histograms and 37 per cent for patients with abnormal patterns. These results demonstrate that nuclear deoxyribonucleic acid ploidy measured by flow cytometry is an important variable in the classification and determination of prognosis for patients with clear cell renal carcinoma.  相似文献   

4.
Prognostic factors in transitional cell carcinoma of the upper urinary tract were assessed with histopathological examination and flow cytometric analysis in a series of 127 patients operated upon between 1976 and 1988. In particular, we evaluated the usefulness of flow cytometry to identify patients who require adjuvant treatment among those with low grade and low stage disease (51% in this series). A multivariate analysis was done on 92 cases, considering patient age and sex, stage, grade and number of lesions (unifocal versus multifocal), site (renal pelvis versus ureter), presence of vesical tumors, recurrences along the urinary tract or in the bladder, type of operation and nuclear deoxyribonucleic acid (DNA) ploidy (diploid versus tetraploid/aneuploid tumors). Only the stage (p = 0.001), grade (p = 0.001) and, to a lesser extent, the DNA pattern (p = 0.031), as well as the number of lesions (p = 0.061) were determinant for prognosis. In regard to the subgroup of 41 patients with grade 2 or less, stage P1 or less tumors, no significant difference in survival was demonstrated between diploid and nondiploid tumor patients. However, 7 of 10 patients from the latter group are still under observation. Therefore, our conclusions may have to be modified in the future.  相似文献   

5.
We studied 100 cases of squamous cell carcinoma of the bladder by flow cytometry after cystectomy. Tumors were classified according to the deoxyribonucleic acid profile into diploid or aneuploid. Proliferation of the tumors was assessed from the proportions of S-phase cells. The flow cytometric data were correlated to the histopathological stage and grade. Grade 1 tumors could be subdivided into diploid and aneuploid in 60 and 40% of the cases, respectively, while 95% of the grade 2 and all grade 3 tumors were aneuploid. Diploid tumors had low proliferation rates, while aneuploid tumors had significantly higher values. A high frequency of muscle invasive diploid squamous cell tumors was noted. Tumor heterogeneity was studied by comparing cell material from superficial and deep tumor areas, which were in agreement in 77% of the cases. By comparing biopsy material with that obtained by bladder washings, biopsy material yielded better information regarding deoxyribonucleic acid ploidy in half of the aneuploid tumors. These results indicate that flow cytometry offers an additional objective method to characterize squamous cell carcinoma.  相似文献   

6.
In 55 patients with urothelial carcinoma of the renal pelvis or ureter, the ploidy, the DNA heterogeneity and the counts of cell cycle phases in the tumor were examined by means of single-cell DNA cytophotometry in order to find more prognostic factors than those already known (stage and grade). Follow-up periods ranged from 1 to 6 years. At the time of first diagnosis, 42 (76%) of the patients had tumors of the renal pelvis, 13 (24%) of them had ureteral tumors. 23 (42%) patients were in stage pT 1 N 0, 15 (27%) in stage pT 2 N 0, 12 (22%) in stage pT 3 N 0, and 5 (9%) were in stage pT 3 N+. The histological malignancy grade most frequently seen in the patients examined--i.e. in 51% of cases--was malignancy grade II. 25% of the patients had grade III tumors whereas only 24% had grade I tumors. With malignancy grade I, DNA cytophotometry showed DNA frequency peaks to be in the diploid range while tumors with malignancy grade II showed heterogenous DNA patterns. 71% of the patients with malignancy grade III showed aneuploid DNA values; 29% of them had polyploid DNA values. For malignancy grades II and III, the proliferation rate of the tumor cells was statistically significantly higher than for malignancy grade I. The determination of tumor heterogeneity and tumor cell proliferation by means of DNA cytophotometry gives valuable clues regarding prognosis.  相似文献   

7.
Tumor deoxyribonucleic acid (DNA) content was analyzed by flow cytometry in 60 consecutive patients with stage I renal cell carcinoma. Of 59 evaluable tumors 27 (46%) were homogeneously diploid, 1 (2%) was tetraploid and 31 (52%) were aneuploid. Of the 32 nondiploid tumors 25 were heterogeneous concerning ploidy. One of the 27 patients with diploid tumors had metastases compared to 5 of the 32 patients with nondiploid tumors (not significant). There was a significant difference in survival between patients with diploid and nondiploid tumors (p = 0.043). Neither nuclear grade, tumor cell type nor tumor size correlated with survival. Analysis of DNA content seems to predict survival significantly for patients with stage I renal cell carcinoma.  相似文献   

8.
Flow cytometry was used to analyze deparaffinized primary renal cell carcinoma specimens from 106 patients to evaluate deoxyribonucleic acid ploidy as a predictor of disease progression and survival. Of these specimens 62 (58%) demonstrated aneuploid stem lines: 30 (48%) of these were tetraploid aneuploid while 32 were nontetraploid aneuploid. Two or more specimens were analyzed from a single primary tumor in 17 patients and heterogeneity of ploidy status was observed in 5 (30%). Specimens of the primary tumor, and regional and/or distant metastases from 11 patients were analyzed; 5 (45%) demonstrated discordance between the ploidy of the primary and the metastatic site. A significant correlation was noted between the presence of aneuploid stem lines and high stage disease (p equals 0.004) but there was no significant correlation between ploidy status and tumor grade. Although there was a significant difference (p equals 0.037) in the incidence of disease progression in patients with diploid tumors (13%) versus those with aneuploid tumors (35%) in the total population, and Kaplan-Meier disease-specific survival curves demonstrated a survival advantage for patients with diploid tumors in the total population, no clear survival advantage was demonstrated for evaluable patients with diploid tumors when controlled for tumor, nodes and metastases stage. In conclusion, the heterogeneity of ploidy status in primary renal cell carcinoma, the high incidence of disease progression in patients with diploid primary tumors and the lack of a clearly demonstrable stage-independent impact of ploidy on prognosis currently would not support widespread clinical application of ploidy status of the primary tumor in the management of individual patients with renal cell carcinoma.  相似文献   

9.
PURPOSE: Squamous cell carcinomas of the renal pelvis and ureter are rare. We report a large series of patients and compare it to patients with urothelial carcinoma. MATERIALS AND METHODS: The initial material was comprised of 808 patients with renal pelvis or ureteral cancer. A review of the histopathological material and clinical records was performed. RESULTS: Only 2 (4%) of 65 patients with squamous cell carcinoma had stage pTa/pT1/pT2 tumors compared to 460 (62%) of 743 patients with urothelial carcinoma. Median survival was much shorter for surgically treated patients with squamous cell carcinoma compared to those with urothelial carcinoma (7 vs 50 months). However, there was no significant difference in the disease specific 5-year survival rate between patients with squamous cell carcinoma and urothelial carcinoma in the same disease stage. Vascular invasion, microscopic solid tumor pattern and large tumor size had negative prognostic significance in multivariate analyses. Histopathological tumor type (squamous cell carcinoma or urothelial carcinoma) had no prognostic significance. CONCLUSIONS: The prognosis for squamous cell carcinoma is poor, but stage for stage the prognosis is not different between patients with urothelial carcinoma and squamous cell carcinoma of the renal pelvis and ureter. It can be presumed that high stage squamous cell carcinoma and urothelial carcinoma become symptomatic first at a time when the tumors already are large, deeply invasive and most often incurable. New treatment modalities are urgently needed to improve the poor prognosis in patients with advanced stage squamous cell carcinoma and urothelial carcinoma of the upper urinary tract.  相似文献   

10.
A total of 50 patients with primary transitional cell carcinoma of the upper urinary tract underwent deoxyribonucleic acid ploidy characterization by flow cytometric analysis of paraffin embedded specimens. The primary tumor was diploid in 29 patients (58%) and aneuploid in 21 (42%). Aneuploidy was identified more frequently in grade 3 than in grades 1 and 2 neoplasms (p = 0.001). Additionally, grade 3 neoplasms occurred more often with invasive (stages T2 to T3) compared to superficial (stages TA, TIS and T1) tumors (p = 0.002). However, deoxyribonucleic acid ploidy was not significantly associated with tumor stage. Among the 49 patients treated by a definitive operation the median survival free of disease and median over-all survival were 33.7 and more than 120 months, respectively. Variables examined included deoxyribonucleic acid ploidy, tumor grade, tumor stage, primary tumor site and type of operation. In the univariate analysis deoxyribonucleic acid ploidy was the only significant predictor of survival free of disease (p = 0.04). Aneuploid tumors had a median survival free of disease of 19 versus 59 months for diploid tumors. However, in the multivariate analysis of factors affecting survival free of disease, the type of operation performed was the only significant variable. Patients undergoing nephroureterectomy with en bloc bladder cuff excision had a favorable survival free of disease (p = 0.04). Tumor stage was the only significant factor associated with over-all survival in univariate and multivariate analyses (p = 0.02 and 0.005, respectively). Patients with superficial tumors had a median survival of more than 120 versus 72 months for patients with invasive tumors. The data suggest that deoxyribonucleic acid ploidy may be a useful parameter to identify risk groups and plan the management of patients with primary transitional cell carcinoma of the upper urinary tract.  相似文献   

11.
Flow cytometric analysis of DNA ploidy was performed on prostatic adenocarcinoma specimens from 80 patients. In all these patients a radical retropubic prostatectomy had been performed. The nuclei for DNA ploidy determination were extracted from paraffin-embedded material of whole sections of the prostate from patients treated by radical prostatectomy between 1980 and 1985. DNA ploidy was a strong prognostic indicator independent of tumor grade and tumor stage. DNA ploidy offered additional information on both tumor stage and tumor grade. In stage C disease the likelihood of progression-free survival was 89.5% in diploid tumors and 27.8% in aneuploid tumors after 9 years. In tetraploid tumors all patients progressed after 9 years. The computed survival rates in stage C disease showed that patients with diploid tumors did significantly better than those with aneuploid or tetraploid tumor patterns. These data indicate therefore that DNA ploidy patterns determined by flow cytometric analysis provide important additional prognostic information on prostatic adenocarcinoma treated by radical prostatectomy.  相似文献   

12.
Flow cytometric nuclear deoxyribonucleic acid ploidy analysis was done successfully on 38 specimens of primary bladder adenocarcinoma treated between 1954 and 1985. Of the specimens 10 (26%) were deoxyribonucleic acid diploid, 8 (21%) were tetraploid and 20 (53%) were aneuploid. Distribution of ploidy patterns between the 14 histological low grade and 24 high grade tumors was similar. Of 38 tumors 35 (92%) showed muscle invasion. One tumor arose in a previously exstrophied bladder, 10 were of urachal origin and 27 arose in an anatomically normal bladder. Of the urachal origin tumors 80% were deoxyribonucleic acid aneuploid. At 5 and 10 years after diagnosis 80 and 70%, respectively, of the patients with diploid tumors were free of disease. By contrast, at 5 and 10 years after treatment only 20 and 12%, respectively, of the patients with nondiploid tumors have not had disease progression (p less than 0.001 log-rank test). None of the 6 patients with diploid, high grade, high stage, muscle invasive tumors had subsequent progression. In contrast, 16 of 17 patients (94%) with high grade, high stage, nondiploid tumors had either local or distant tumor recurrence (p less than 0.0005). Nuclear deoxyribonucleic acid ploidy pattern appears to be the most significant prognostic information currently available to stratify expected prognosis for patients with muscle invasive adenocarcinoma of the bladder. This test probably should be a standard tool in the clinical management of patients with this rare bladder malignancy.  相似文献   

13.
D S Yu  J Wang  S Y Chang  C P Ma 《European urology》1991,20(3):227-231
In 5 patients with sarcomatoid renal cell carcinoma, the nuclear DNA content and size were determined by flow cytometry (FCM), and the prognostic value of DNA ploidy, the percentage of S-phase cells (SPF), and the ratio of modal nuclear size with clinicopathologic behavior was analyzed. Age and clinical stage have been shown to have a strong correlation with prognosis. Older patients with a high stage of cancer had poor outcome with a shorter survival time. In all 60% of the tumors were aneuploid. Tumor invasiveness was related to DNA ploidy. With increasing stage, the overall incidence of aneuploid rises. One alive patient had diploid DNA while 75% of the patients who died of sarcomatoid renal cell carcinomas had aneuploid DNA. Diploid sarcomatoid renal cell carcinomas show significantly lower SPF than aneuploid tumors. There was no significant association between the modal nuclear size and the invasiveness of tumors or survival time. This study suggests that FCM analysis of tumor DNA content and cell cycle could be regarded as an additional prognostic determinant of sarcomatoid renal cell carcinoma.  相似文献   

14.
OBJECTIVE: The prognostic value of deoxyribonucleic acid (DNA) ploidy in renal cell carcinoma (RCC) is not well-defined among modern surgical nephrectomy series. We sought to determine which variables correlated with overall survival and recurrence-free survival in the modern era. METHODS: We reviewed all patients from 1992 to 2000, who prospectively had DNA ploidy analysis of their primary tumor determined at the time of nephrectomy for nonmetastatic RCC. Variables examined included age, gender, ethnicity, presentation (incidental vs. symptomatic), preoperative laboratory studies, American Society for Anesthesiology class, tumor size, tumor-nodes-metastasis stage, histology, Fuhrman grade, and diploid versus nondiploid tumor. Statistical analyses of overall survival and recurrence-free survival were performed using the Kaplan-Meier method, log-rank test, and Cox regression model using commercially available software. RESULTS: Sixty men and 41 women, median age 61 years (range, 23-85), were included. Pathologic stage included T1 (54 patients), T2 (14), and T3 (33). Eighty-four patients had conventional RCC. A total of 58 patients had well-differentiated (Fuhrman Grade 1 [12] or Grade 2 [46]), 28 had moderately differentiated (Grade 3), 12 had poorly differentiated tumors (Grade 4), and 3 were not specified. There were 52 patients who had diploid tumors, and 49 had aneuploid tumors. Median follow-up was 39 months (range, 0-109). Actuarial 5-year overall survival was 70%, and 5-year recurrence-free survival was 76%. Diploid tumors were significantly associated with better recurrence-free survival (P = 0.02) but not overall survival (P = 0.17). On multivariate analysis, the American Society for Anesthesiology class (P = 0.01), abnormal preoperative platelet count (P = 0.03), and tumor differentiation (P = 0.01) were independent predictors of overall survival, whereas only tumor differentiation (P = 0.05) was an independent predictor of recurrence-free survival. CONCLUSIONS: In the modern era, DNA ploidy is not an independent predictor of either overall survival or recurrence-free survival in patients with nonmetastatic RCC. The most important predictor of recurrence-free survival is tumor differentiation.  相似文献   

15.
IntroductionMore than 40% of patients with renal cell carcinoma present with disease progression after surgery. The objective of the current study was to identify a clinically useful set of prognostic factors that would correlate significantly with the capacity of progression.Material and methodsThe authors studied 252 patients with renal cell carcinoma who underwent radical nephrectomy. Followup ranged from 12-246 months (median 36 months). Several morphologic parameters of the tumors were considered. DNA content was analyzed by flow cytometry and tumor size was determined from the surgical specimen. A Cox proportional hazards regression model was used to identify significant independent prognostic factors for disease progression.ResultsA total of 224 out of 252 were available for suitable histograms. Of the 224 patients, 95 (42,4%) were aneuploid tumors, 106 (47,2%) were organ-confined renal cell carcinoma and 87 (39,74%) presented disease progression. At 5 and 10 years of followup, disease free survival was found to be 66,31% and 62,23%, respectively. Univariate analysis revealed that DNA ploidy, Furhman grade and stage (TNM) had a statistically significant predictive value for disease progression. Survival univariate analysis found a worse probability of survival for aneuploid tumors, grade III-IV tumors, non organ-confined tumors and conventional and undiferentiated tumors. Using multivariate survival analyses, Furhman grade, stage (TNM) and DNA ploidy were the only independent prognostic factors. So, the probability of death for aneuploid tumor was 1,7 times higher than for diploid tumors.ConclusionsStage, DNA content and Furhman grade were the only significant independent predictors of disease progression. Tumoral size and histological type did not provide more additional information.  相似文献   

16.
We selected for a prospective surveillance study 167 patients with untreated grades 1 and 2 prostate cancer. The tumors were classified regarding modal deoxyribonucleic acid value (ploidy) by flow cytometry, cytological grade by transrectal fine needle aspiration biopsy and local tumor stage. Of the patients 146 could be evaluated. Mean followup was 50 months. The initial ploidy was statistically correlated to cytological grade but not to initial local tumor stage, prostatic acid phosphatase activity or patient age. Initial ploidy and cytological grade had a prognostic value regarding local tumor progression when considered as single predictors and in combination. Two patients with diploid and 8 with nondiploid tumors initially had metastases during the surveillance. Five patients (1 with diploid and 4 with nondiploid disease) died of prostatic cancer. Modal deoxyribonucleic acid value and cytological grade were of prognostic value in untreated prostate cancer.  相似文献   

17.
A total of 22 patients with high grade P2-4N+ transitional cell carcinoma of the bladder underwent flow cytometric analysis of nuclei obtained from paraffin embedded specimens from the primary (bladder) and metastatic (lymph node) sites. Tumor heterogeneity was defined as polyclonal aneuploidy of the primary tumor (not identified in the population studied) or as a difference in the deoxyribonucleic acid index of the primary and metastatic sites of 0.20 or more (8 patients). With these criteria 8 patients (36%) had heterogeneous tumors and 14 (64%) had homogeneous tumors. The median survival of 14 patients with aneuploid and 8 with diploid primary tumors was 17.5 and 8.0 months, respectively (p equals 0.08, Lee-Desu test). When patient survival was compared to the ploidy of the metastatic site, or in patients with diploid primary and metastatic lesions versus deoxyribonucleic acid aneuploidy at either the primary and/or metastatic site, the aneuploid tumors had a longer survival but this difference was not significant (p equals 0.13 and 0.23, respectively). Our study demonstrates the value of flow cytometry to identify primary metastatic tumor heterogeneity. It also suggests that the presence of metastasis may be a more important factor to define the biological potential of transitional cell carcinoma than is deoxyribonucleic acid ploidy.  相似文献   

18.
H Al-Abadi  R Nagel 《European urology》1988,15(3-4):271-276
In 112 patients with renal cell carcinoma, the ploidy, DNA heterogeneity and the phases of the cell cycle occurring in the tumors were determined by means of single-cell DNA cytophotometry, in order to establish further prognostic factors in addition to the ones known so far (stage/grade). Patients with aneuploid tumors or tumors with more than one DNA frequency peak were found to have lymph node metastases intraoperatively and died earlier than patients with diploid tumors. Patients who had tumors with low proliferative activity survived longer than patients with highly proliferative tumor activity (p = 0.001).  相似文献   

19.
In 157 patients with renal cell carcinoma, the ploidy, DNA heterogeneity and the phases of the cell cycle occurring in the tumors were determined by means of single-cell DNA cytophotometry, in order to establish further prognostic factors in addition to the ones known so far (stage/grade). Patients with aneuploid tumors or tumors with more than one DNA frequency peak were found to have lymph node metastases intraoperatively and died earlier than patients with diploid tumors. Patients who had tumors with low proliferative activity survived longer than patients with highly proliferative tumor activity (p = 0.001).  相似文献   

20.
Sixty-eight patients with transitional cell carcinoma of the renal pelvis were studied with respect to clinical presentation, tumor grade, stage and location, subsequent development of other urothelial tumors, and patient survival. Of the 66 patients with adjacent mucosa available for evaluation, 63 (95 per cent) had abnormal findings with severe dysplasia and CIS common in the high-grade, high-stage tumors. Twenty-eight patients (41 per cent) had transitional cell carcinoma previously, concomitantly, and/or subsequently, and in 14 patients (21 per cent) subsequent bladder tumors developed. Because of the relatively high tumor recurrence rate in the ureter (16 per cent) in patients who underwent subtotal ureterectomies, nephrectomy and complete ureterectomy including a bladder cuff should be the operation of choice in patients with carcinoma of the renal pelvis.  相似文献   

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