Initial high-grade T1 urothelial cell carcinoma: feasibility and prognostic significance of lamina propria invasion microstaging (T1a/b/c) in BCG-treated and BCG-non-treated patients

OBJECTIVES: This study aimed to determine the prognostic value of depth of lamina propria invasion in initial high-grade T1 bladder tumors. Secondary aims were to evaluate the prognostic significance of concomitant carcinoma in situ (CIS) and the impact of bacillus Calmette-Guérin (BCG) treatment as well as to assess the feasibility of microstaging by pathologists in a community setting. PATIENTS AND METHODS: Ninety-seven tumors were available for study and were substaged according to invasion superficial to, into or beyond the muscularis mucosae (MM) (T1a, T1b, T1c). Outcomes were compared by chi-square analysis. Recurrence-free and progression-free survival estimates were obtained by Kaplan-Meier analysis. BCG treatment impact and prognostic significance of CIS were also evaluated (Cox regression). RESULTS: T1 subclassification was possible in 87% (85/97) of cases: 38 (39.1%) T1a, 10 (10.3%) T1b, and 37 (38.1%) T1c; in 12 patients (12.4%) substaging was not possible. Mean age was 66.4 years and mean follow-up was 53 months. Recurrence rates were similar for all groups. By contrast, the progression rate for deep lamina propria-invasive tumors, i.e. T1b and T1c, was 34% (16/47) in comparison to 8% (3/38) for T1a (p=0.016). Progression-free intervals were significantly different in patients with (T1b, T1c) or without (T1a) deep lamina propria involvement (p=0.003), regardless of BCG treatment (p=0.02). BCG-treated patients (67 cases) showed a slight trend towards a better outcome, but differences were not significant. CIS was associated with more than 50% of cases that progressed. On multivariate analysis, depth of invasion and CIS remained two independent prognostic factors, increasing the hazards ratio of progression to 4.47 and 3.19 respectively. CONCLUSIONS: The depth of invasion in the TURB specimens is an independent prognostic factor for T1 bladder cancer even in BCG-treated patients. Associated CIS significantly increases the risk of progression in these patients. The percentage of cases that can be substaged according to the depth of lamina propria involvement increases over time with the collaboration between urologists and pathologists. Consequently, we support that routine pathological assessment of the level of MM invasion in patients with stage T1 bladder cancer should be included in the histopathological report.     

Pretreatment p53 nuclear overexpression as a prognostic marker in superficial bladder cancer treated with Bacillus Calmette-Guérin (BCG)

INTRODUCTION: Altered p53 gene product correlates with the stage and grade of bladder tumor, but its value as a predictor of BCG response has been disappointing. In order to revisit the prognostic value of pretreatment p53 nuclear overexpression for the BCG response, we studied a large cohort of consecutive patients with superficial bladder cancer treated with BCG. METHODS: From 1988 to 2001, 102 patients with a history of multifocal, recurrent, and/or high-risk papillary transitional cell carcinoma or carcinoma in situ, were treated for the first time with BCG. p53 immunostaining was performed on paraffin-embedded tissues using monoclonal antibody DO7 and an automated immunostainer. Special attention was paid to the conditions of tumor fixation. p53 overexpression was defined as more than 20% tumor cells with p53-stained nuclei. RESULTS: Immunostaining was significantly higher for Ta/T1 G3 +/- Cis (p < 0.001), tumoral substage T1b (p = 0.001), grade 3 (p = 0.0001), and Cis (p = 0.002). Times to recurrence, progression and cancer death were shorter among patients with p53 overexpression (p = 0.03; p < 0.0001; p = 0.0003). In multivariate analysis, p53 overexpression was an independent predictor of recurrence (p = 0.0003) [RR = 0.15; 95%CI, 0.06 to 0.42]. CONCLUSION: Pretreatment p53 nuclear overexpression in superficial bladder tumors is associated with a high risk of disease recurrence, progression and cancer death after BCG therapy. Applying antibody DO7 with an automated immunostainer and stringent fixative conditions, p53 nuclear immunostaining yields clinically relevant information and may be a useful tool for selecting patients with superficial bladder cancer who might be resistant to BCG.     

Microstaging of pT1 transitional cell carcinoma of the bladder. Does it really differentiate two populations with different prognoses? (pT1 subcategory)

INTRODUCTION: Our objective was to evaluate the feasibility and value of microstaging in pT1 transitional cell carcinoma (TCC) of the bladder in a well-defined group of patients treated with transurethral resection (TUR) only. MATERIALS AND METHODS: The clinical records of 152 patients who underwent TUR for the treatment of primary superficial TCC of the bladder between 1983 and 1997 were reviewed. Patients with primary carcinoma in situ and who received adjuvant intravesical treatments were excluded from study. We subclassified the pT1 tumors into two groups according to muscularis mucosae (MM) invasion (pT1 and pT1b). The recurrence and progression rate of cancers was analyzed according to the stage, grade, multiplicity and tumor size. Mean follow-up was 68 months. Estimation of the cumulative distribution of the disease-free interval in separate groups was calculated according to the Kaplan-Meier method. Multivariate analysis of the data was performed by using Cox regression method. A value of p < 0.05 was taken to be statistically significant with odds ratios. RESULTS: Of the 152 patients, tumor stage was pTa in 62 (40.8%) patients and pT1 in 90 (59.2%) patients. Among those pT1 tumors, MM was identified in 50 (55.5%) of cases (pT1a = 34, pT1b = 16). In the remaining 40 (44.5%) patients, MM could not be assessed. Kaplan-Meier analysis revealed that recurrence and progression were statistically significant for stage, multiplicity and grade of tumor. However, multivariate analysis revealed that stage was the only prognostic factor for recurrence and progression (p = 0.0001). CONCLUSION: The present study underscores the fact that pT1b tumors have a distinct natural history. If initial conservative treatment is selected, the patients must be followed very cautiously.     

Prognostic Significance of p53 Protein Accumulation in Stage pT1 Transitional Cell Carcinoma of the Bladder

Objective: Mutations in the tumour suppressor gene p53 results in the production of a mutant type, dysfunctional p53 protein which can readily be detected in the cell nucleus by immunohistochemical staining. This study aims to investigate the association of nuclear p53 protein accumulation with the clinical outcome of stage pT1 transitional cell carcinoma of the bladder which is renowned for high rates of recurrence and progression. Methods: TUR samples of the tumours from fifty-two patients with primary stage T1 bladder cancer were analyzed immunohistochemically using the standard avidin-biotin peroxidase method for nuclear p53 accumulation. Status of p53 immunostaining was correlated with tumour recurrence, disease progression and three-year survival of each patient. Results: The rate of tumour recurrence in pT1 bladder cancer was 36% in patients with tumours stained negatively for p53 protein and 78% in patients with tumours stained positively for p53 protein. Disease progression was seen in 15% of p53 (-) patients and in 56% of p53 (+) patients. Conclusions: In stage pT1 bladder tumours p53 nuclear accumulation indicates higher rates of tumour recurrence and disease progression. Accordingly, in patients who have pT1 bladder tumours with nuclear p53 accumulation, institution of more aggressive therapy should be considered and early radical therapeutic modalities should be offered to these patients.     

Prognostic value of MCM2 immunoreactivity in stage T1 transitional cell carcinoma of the bladder

OBJECTIVE: Due to the heterogeneous biologic behavior of stage T1 bladder carcinomas, there is a need for new markers allowing to assess the prognosis more accurately. To our knowledge, there are no reports on studies investigating minichromosome maintenance protein 2 (MCM2) expression in bladder carcinomas. Thus, we investigated the prognostic value of MCM2 immunoreactivity in stage T1 bladder tumors. METHODS: Fifty-four tumors were analyzed using Biochip microarrays. Also p53 and Ki67 antigen expression were examined. Immunohistochemical scores were compared with the clinical outcome. RESULTS: During a median follow-up of 43 months, tumor recurrence was registered in 43 and progression to stage T2 in 19 patients. Kaplan-Meier curves demonstrated that high-level MCM2 expression was significantly associated with early tumor recurrence when using a cutoff of 60% (p=0.0035 by log-rank test), and with early tumor progression when using a cutoff of 20% (p=0.0454). There was no relationship (p=0.604) between MCM2 and p53, but a tendentious relationship (p=0.082) between MCM2 and Ki67 antigen expression. MCM2 (p=0.006), Ki67 antigen (p=0.035) and p53 expression (p=0.049) as well as tumor grade (p=0.026) and age (p=0.025) were found significantly associated with recurrence-free survival by univariate Cox regression analysis, among which only Ki67 antigen expression (p=0.015) and age (p=0.019) proved to be of independent predictive value by multivariate analysis. Concerning tumor progression, MCM2 expression was identified as the only predictive parameter by log-rank test, but it was not of independent predictive value by multivariate analysis (p=0.101). CONCLUSION: Our data suggest that MCM2 expression may bear some prognostic relevance in stage T1 bladder carcinomas.     

Evaluation of p53 nuclear accumulation in low- and high-grade (WHO/ISUP classification) transitional papillary carcinomas of the bladder for tumor recurrence and progression

OBJECTIVES: To evaluate the association of p53 nuclear accumulation with recurrence and progression in transitional cell carcinomas of the bladder and to examine the distribution of p53 in low-grade and high-grade transitional cell carcinomas according to the World Health Organization/International Society of Urological Pathology classification. PATIENTS AND METHODS: Nuclear accumulations of p53 were examined in a total of 99 patients with transitional cell carcinoma between May 1995 and October 1999. The mean age was 64 years. There were 94 (95%) men and 5 (5%) women. Following resection, surgical specimens were examined, and p53 accumulation with a 20% cutoff value was accepted as positive staining. Of the 99 patients, 52 (53%) had histologically superficial bladder tumors, and 47 (47%) had invasive tumors. Data concerning grade, stage, number of recurrences, and disease progression were available for each patient. RESULTS: The median follow-up period was 55 months. 60 of the 99 patients (61%) had p53 overexpression. The difference for p53 overexpression between low-grade and high-grade tumors was significant (p < 0.05). In low- and high-grade tumors, there was no significant relationship for recurrence between p53-positive and p53-negative groups. But there was a statistically significant relationship between progression and histological grade of the tumors. p53 had no significant relationship with tumor recurrences (p > 0.05), but its relationship with progression was statistically significant (p < 0.05). CONCLUSIONS: We did not find a correlation between tumor recurrence and p53 overexpression, but p53 overexpression has a predictive value in determining tumor progression. High-grade tumors had higher p53-positive values than low-grade tumors. This group of patients should be considered for radical therapies on the basis of other prognostic parameters.     

IMMUNOHISTOCHEMICAL DETECTION OF p53 PROTEIN OVEREXPRESSION VERSUS GENE SEQUENCING IN URINARY BLADDER CARCINOMAS

PURPOSE: Mutations of p53 tumor suppressor gene and nuclear accumulation of p53 protein are common in bladder tumors. The prognostic significance of p53 alterations in bladder tumors has not been established. The aim of the present study was to evaluate an immunohistochemical (IHC) method for the routine determination of p53 protein overexpression in human bladder tumors and to determine the relation between nuclear accumulation of p53 with the traditional prognostic indicators and patient survival. MATERIALS AND METHODS: 104 transitional cell carcinomas of the bladder were analyzed simultaneously by immunohistochemistry for p53 protein overexpression and direct DNA sequencing for p53 gene mutations. RESULTS: The overexpression of p53 protein was reported in 30.8% of the cases and mutations of p53 gene in 23.0%. A significant association was observed between p53 alterations established either by IHC or direct DNA sequencing and stage (p<0.0001), grade (p<0.001), vascular invasion (p = 0.0005), DNA ploidy (p = 0.0002) and carcinoma in situ (p<0.0001). The correlation between the p53 gene mutations and p53 nuclear reactivity as detected by IHC was highly significant (p<0.0001). Univariate statistical analysis showed that the expression of p53 was significantly correlated to poor prognosis (p<0.0001). However, in multivariate analysis, only stage was significantly correlated to prognosis (p<0.0001). CONCLUSIONS: The IHC method was highly sensitive and specific and simple to apply for the routine examination of p53 overexpression in bladder tumors. However, overexpression of p53 as determined immunohistochemically, does not appear to have a better predictive prognostic value than stage in bladder tumors.     

膀胱癌p53蛋白核蓄积的临床意义

为探讨不同病理分期膀胱癌p53蛋白核蓄积与肿瘤恶性进展的关系．采用免疫组织化学方法检测122例获随访结果的膀胱癌患者的p53表达，用多变量相关分析，Logistic回归分析和Kaplan-Meier法分析。发现p53蛋白核反应与肿瘤临床病理分期及淋巴结转移呈正相关(P=0.003)；Kaplan—Meier生存分析显示肿瘤局限于膀胱内(P1，P2和P3a)，p53蛋白阳性染色者复发率显著高于阴性者，5年生存率明显低于阴性者。本研究证明p53蛋白核蓄积表示肿瘤呈恶性进展，病人预后较差。     

Predictive value of progression of muscularis mucosae and percentage G3 cells in vesical TIG3 tumours

Introduction and objectiveVesical tumor T1G3 constitutes the border between the superficial tumor and the infiltrante tumor. Some of these tumors do not respond to BCG and progress, with cystectomy that present poor results, patients who would benefit from a precocious and aggressive treatment if we could identify them in an preinvasive stage. New predictive factors try to select to these tumors, being little the works that consider anatomo- pathological meticulous study (substanding of the T1 in T1a and T1b and percentage of present G3 cells in the tumor). Our objective is to analyze the value of these anatomo-pathological considerations like predictive factors of progression.Material and methodsRetrospective study of a series of 91 patient affection of vesical tumor T1G3 with initial treatment by means of RTU and BCG. We analyzed 12 variables. The new predictive factors: the level of invasion respect to muscularis mucosae and the percentage of G3 cells. By means of logistic regression analisys we establish the independent pronostic factors for tumoral progression.ResultsA total of 31 patients presented infiltration of detrusor, passing away 17 of tumoral cause, after an average time of pursuit of 57.8 ± 28.2 months. In 8 cases (9%) the substanding could not be determined. The rate of progression for T1a tumors was of 20% (8/40) and for T1b 53% (23/43). Presented independent predictive value of progression the multiplicity (odds: 7,26), the size (odds: 2,14), the presence of Cis (odds: 1,42) and the subestanding (odds: 6,81).ConclusionThe substanding is a predictive factor of progression clinically useful in vesical tumors T1G3, reason why we considered habitual clinical introduction.     

Outcomes after intravesical bacillus Calmette-Guerin are not affected by substaging of high grade T1 transitional cell carcinoma

PURPOSE: Substaging of T1 bladder tumors into T1a and T1b based on invasion of the tumor superficial to and beyond the muscularis mucosa has been assigned prognostic significance. We determined whether outcomes after intravesical bacillus Calmette-Guerin (BCG) differ between stage T1a and T1b subcategories. MATERIALS AND METHODS: Retrospective pathological evaluation of the initial transurethral resection specimens of stage T1 bladder tumors was performed by 2 pathologists. Grade 1, 2 or 3 and stage T1a or T1b were assigned to each case. Followup was from the date of transurethral resection to date of death or the last visit. Kaplan-Meier probability and log rank test were used to evaluate recurrence and progression. RESULTS: Substaging was performed in 49 of the 55 patients (89%) with stage T1 disease. Disease was stage T1a in 32 (65%), stage T1b in 17 (35%), grade 3 in 45 (92%) and grade 2 in 4 (8%) cases. Maximum followup was 147 months (median 71) and 28 cases had a minimum of 5 years of followup. Recurrence was noted in 33 cases (67.3%), including 22 stage T1a (69%) and 11 stage T1b (65%), at a median followup of 11.3 and 8.6 months, respectively. Progression to a higher stage of disease was recorded in 12 cases (24.4%), including 7 (22%) stage T1a and 5 (29%) stage T1b, at a median followup of 108 and 120 months, respectively. The difference between T1a and T1b subcategories was not statistically significant in regard to recurrence-free (p = 0.7203) and progression-free (p = 0.574) outcomes. CONCLUSIONS: Substaging of T1 tumors did not affect response to BCG in regard to recurrence or progression. Therefore, intravesical BCG is effective for stages T1a and T1b disease.     

Prospective evaluation of p53 as a prognostic marker in T1 transitional cell carcinoma of the bladder

OBJECTIVE: To prospectively evaluate p53 overexpression as a predictor of survival in patients with a first diagnosis of T1 transitional cell carcinoma (TCC) of the bladder, as several reports implicate p53 as an important prognostic marker for progression and survival, but all previous studies were retrospective, giving conflicting and irreproducible results, rendering inappropriate any attempt at integrating p53 into clinical decision-making. PATIENTS AND METHODS: Patients with a first diagnosis of T1 TCC of the bladder were enrolled; p53 overexpression was assessed by immunohistochemistry (IHC) using both monoclonal antibody 1801 and DO7. The pathological stage and IHC score were assigned by one pathologist, and the markers were scored categorically. RESULTS: Of the 89 patients who were evaluable, 53 had p53-positive tumours. The median follow-up for the survivors was 52 months. Eighty-two patients had high-grade tumours, using the World Health Organisation/International Society of Urological Pathology 1998 grading system. Fifty-eight patients had unifocal tumours and 34 had associated carcinoma in situ. The 3 year and 5 year overall survival rates were 81% (95% Cl: 73%, 90%) and 68% (95% Cl: 56%, 80%) respectively. The 3 year and 5 year disease specific survival rates were 87% (95% Cl: 79%, 94%) and 79% (95% Cl: 70%, 89%) respectively. There was no difference in disease-specific survival between patients with and without p53 over expression (p=0.56) [corrected] CONCLUSIONS: p53 tissue typing by IHC in a prospective cohort of patients with T1 bladder cancer was not clinically useful as a prognostic marker in a contemporary series of T1 tumours.     

p53 expression predicts progression and poor survival in T1 bladder tumours

OBJECTIVES: Histological grade (G) is the only parameter proved to have prognostic value for progression in T1 transitional cell carcinoma (TCC) of the bladder, although it is considered inaccurate to make clinical decisions on individuals. The aim of the present study was to evaluate the prognostic relevance of p53 expression in T1 TCC of the bladder. METHODS: Clinical records of 207 patients with T1 TCC of the bladder were reviewed for clinical parameters reported to influence the evolution of superficial bladder cancer. Among these 207 patients, 40 developed muscle-invasive disease (20 G2 and 20 G3). A retrospective case-control study was then carried out comparing the latter 40 tumours with 40 control tumours matched by grade, sex, age, number and size of the tumours, chemical exposure and presence of carcinoma in situ. p53 immunostaining with monoclonal antibody was performed in these two groups. RESULTS: Histological grade was the only clinical parameter that influenced evolution. p53 expression correlated with tumour progression, since it was observed in 21 out of 24 p53-positive tumours and in only 20 of 56 p53-negative tumours (p<0.0001), showing a specificity of 93. 5% and a sensitivity of 53%. p53 expression correlated as well with patient survival, being 39% in patients with p53-positive tumours and 80% in patients with p53-negative tumours at 60 months (p<0. 0001). CONCLUSIONS: p53 protein expression has prognostic value for survival and progression in T1 bladder tumours and can be used for early detection of poor-prognosis T1 bladder tumours.     

Intérêt pronostique de l’infiltration du chorion dans les tumeurs vésicales pT1

IntroductionThe aim of our study was to evaluate the prognostic impact of tumor infiltration depth of the lamina propria and invasion or non-invasion of the muscularis mucosa of pT1 bladder tumors, studying recurrence and progression rate, overall survival, disease-free survival and progression-free survival.Patients and methodsAll slides were reviewed to determine the presence or absence of muscularis mucosa, invasion above (pT1a) or below (pT1b) the muscularis mucosa, and the invasion depth of the lamina propria (pT1m: a single focus of lamina propria invasion ≤0.5 mm, pT1e: single focus >0.5 mm of lamina propria invasion or multiple micro-invasive area).ResultsDepending on the invasion of the muscularis mucosa, the rate of recurrence and progression was more frequent in pT1b tumors in comparison to patients classified pT1a, with a recurrence rate of 84.6% (p = 0.0012) and a progression rate of 38.5% (p = 0.003). Depending on the degree of invasion of the lamina propria, the rate of recurrence and progression was more frequent for pT1e tumors in comparison to pT1m, with a recurrence rate of 57.2% (p = 0.05) and a progression rate of 17.9% (p = 0.11). Disease-free survival was 70.3 months for pT1a tumors against 53.6 months for pT1b tumors (p = 0.046), and it was 61.7 months for pT1e tumors against 55.5 months for pT1m tumors (p = 0.85).ConclusionThe classification of bladder tumors based on the invasion of the lamina propria has proved its efficiency through the recurrence rate and the progression rate among our patients.     

Decreased ezrin and paxillin expression in human urothelial bladder tumors correlate with tumor progression

ObjectivesF-actin binding proteins ezrin and paxillin are involved in cell adhesion and cell migration/invasion. The aim of the study was to investigate their role in urothelial bladder carcinogenesis.Materials and methodsExpression of ezrin and paxillin was studied by immunohistochemistry in 104 and 96 cases of urothelial bladder tumors, respectively. Correlations with clinicopathologic data and expression of p53, E-cadherin, and β-catenin were examined.ResultsPositive ezrin and paxillin protein expression was found in 99% and 93.7% of cases, respectively. Membranous expression of ezrin was significantly lower in high grade tumors and correlated with invasion. Multivariate analysis showed that ezrin is an independent predictor of muscularis propria invasion. Paxillin expression was significantly decreased in urothelial carcinomas compared with tumors of low malignant potential and low paxillin levels also correlated with advancing tumor stage and invasion. A statistically significant correlation was found between membranous ezrin and E-cadherin as well as between ezrin and paxillin expression in urothelial tumors.ConclusionsDown-regulation of ezrin and paxillin in urothelial bladder tumors is associated with aggressive tumor features and invasiveness.     

Relation between cyclooxygenase-2 expression and clinicopathologic parameters with patient prognosis in transitional cell carcinoma of the bladder

OBJECTIVE: To evaluate the correlation between cyclooxygenase-2 (Cox-2) expression and clinicopathologic findings with the effect of these variables on prognosis of bladder cancer. METHODS: Cox-2 expression was examined immunohistochemically in paraffin blocks of 99 patients. Correlations between Cox-2 expression and variables like cancer stage and grade, number of mitoses, angiolymphatic invasion, number and size of the lesions were determined. RESULTS: Cox-2 expression was detected in 52 (52.5%) patients. Univariate regression analysis between Cox-2 expression and clinicopathologic findings showed a significant correlation only in the pathologic stage of the patients (p = 0.048) (OR =2.64, CI = 0.97-7.81). Multivariate regression analysis in stage T1 revealed an increasing number of mitoses as an independent prognostic factor for recurrence (p = 0.002) (OR = 1.5, CI = 1.16-1.92) and progression (p = 0.030) (OR = 8.23, CI = 1.22-55.27) although a prognostic factor was not found for progression in stage T2. CONCLUSION: Univariate analysis showed that only the pathologic stage correlated significantly with Cox-2 expression. Cox-2 expression revealed a significant relation with patient prognosis in stage T2 but not in stage T1. These results support the fact that Cox-2 inhibitors may play a role in progression of invasive bladder tumors.     

膀胱癌中bcl-2和p16基因的表达与预后的关系

目的 探讨ｂｃｌ－２和Ｐ１６基因蛋白在膀胱癌的表达与预后的关系。方法 采用ＳＡＢＣ法对５１例膀胱癌组织和５例正常膀胱粘膜行ｂｃｌ－２和Ｐ１６基因表达的检测。结果 ｂｃｌ－２在膀胱癌的阳性表达率为８０．２％,生存组和死亡组之间比较差异有显著性意义。Ｐ１６在膀胱癌在阳生表达率为５０．９％。５例正常膀胱粘膜均阳性,两者比较有显著性意义。在病理分级、临床分期和预后的总样本率中比较差异有显著性意义;即随病理     

The relationship between the expression of E-cadherin and tumor recurrence and progression in high-grade stage T1 bladder urothelial carcinoma

Objective To evaluate the relationship between the expression of E-cadherin (E-CD) and tumor recurrence and progression in patients with high-grade stage T1 urothelial carcinoma of bladder. Methods Fifty-two patients who had primary high-grade stage T1 urothelial carcinoma were enrolled to the study. The pathologic specimens of patients were evaluated and staged as T1a and T1b according to muscularis mucosae involvement by the tumor. The immunohistochemical demonstration of E-CD was accomplished by using immunoperoxidase method and all the specimens were examined under light microscope for E-CD level. Results The mean age of the patients was 64.0 ± 7.7 (range 36–81) years. The mean follow-up period was 56.4 ± 19.4 (range 14–84) months. Among 52 patients, 27 (52%) of them were stage T1b and 25 (48%) were T1a tumors. The recurrence rates for T1a and T1b groups were 52% (n = 13) and 92.6% (n = 25), respectively (P < 0.05). The expression of E-CD was homogenous in 52% of pT1a and 14.8% of T1b tumors (P < 0.05). In T1a group with recurrence, homogeneous E-CD staining ratio was 30.7% (n = 4/13), but it was 75% (n = 9/12) in T1a patients without recurrence (P < 0.05). In T1b group with recurrence, the homogenous expression of E-CD was 12% (n = 3/25) and the expression of E-CD was heterogenous in 88% (n = 22/25) of them (P < 0.05). In T1a group, progression of the disease was detected in 28% (n = 7/25) of the patients, but disease progression was seen in 55.5% (n = 15/27) of T1b group patients (P < 0.05). In T1a group with progression, heterogeneous E-CD staining ratio was 85.7% (n = 6/7), but it was 80% (n = 12/15) in T1b patients with progression. The effects of tumor number, tumor size and carcinoma in situ presence on recurrence were evaluated within each group. It was determined that parameters such as tumor number and tumor size had no significant effect on recurrence of the groups. The mean survival rates were statistically different between the groups. On multivariate analysis only E-cadherin expression (P = 0.012, odds ratio 6.291, 95% confidence interval for odds ratio 1.303–4.72) and tumor stage (P = 0.003, odds ratio 11.58, 95% confidence interval for odds ratio 2.446–8.542) remained independently significant as predictors of recurrence. Conclusion E-CD expression was decreased in pathologic specimens of bladder tumor patients with muscularis mucosae involvement and this condition correlated well with tumor recurrence.     

Importance of serum p53 antibodies during follow-up after treatment of invasive bladder tumors

INTRODUCTION: To investigate the prognostic importance of the changes in serum p53 antibody titrations during follow-up of patients who had anti-p53 antibody-positive invasive bladder tumors with transitional epithelial cells. MATERIALS AND METHODS: The study group consisted of 23 clinically T3相似文献   

Significance of the depth of tumor invasion and lymph node metastasis in superficially invasive (T1) esophageal adenocarcinoma

Superficially invasive esophageal adenocarcinomas are a heterogeneous group of tumors, including tumors invading into mucosa and submucosa. The prognostic significance of the depth of tumor invasion and lymph node status in this group of patients remain unclear. We evaluated 90 consecutive patients with resected T1 adenocarcinoma of esophagus or esophagogastric junction. The T1 tumors were classified into four groups based on the depth of invasion: T1a, invading into lamina propria; T1b, into muscularis mucosae; T1c, into superficial submucosa; and T1d, into deep submucosa. The depth of tumor invasion was compared with clinicopathologic features. The depth of tumor invasion was significantly associated with the presence of lymph node metastasis (36% in T1d, 8% in T1c, 12% in T1b, and 0% in T1a; P < 0.001) and with tumor size (76% > 1.2 cm in T1d, 75% in T1c, 35% in T1b, and 25% in T1a; P < 0.001). The 5-year recurrence-free and overall survivals were significantly better in patients with tumors confined to mucosa (100% and 91%, respectively) than invasive into submucosa (60% and 58%; P = 0.0005 and P = 0.02, respectively). Lymph node metastasis was associated with tumor recurrence (P = 0.01) but not overall survival. Lymphovascular invasion was associated with both tumor recurrence (P = 0.001) and overall survival (P < 0.001) and was an independent prognostic factor in multivariate analysis (P = 0.04). Our study indicated evaluation of depth of tumor invasion, status of lymph nodes, and lymphovascular invasion is important in resected superficially invasive esophageal adenocarcinoma and may provide supportive information for the decision about postoperative adjuvant therapy.     

Clinical evaluation of serum p53 antibodies in patients with upper urinary tract tumors

PURPOSE: We retrospectively assessed the clinical significance of anti-p53 antibody (S-p53Ab) status in the serum of patients with upper urinary tract tumors. MATERIALS AND METHODS: Enzyme-linked immunosorbent assay was used to analyze S-p53Abs in 63 upper urinary tract tumors. Its incidence and clinical or pathological background were analyzed in comparison with 80 bladder tumors. RESULTS: The prevalence of S-p53Abs in patients with upper urinary tract tumors was higher than that in patients with bladder tumors (27.0% vs 17.5%). Especially, 34.8% of patients showed positive S-p53Abs in invasive upper urinary tract tumors (pT1 or more). In upper urinary tract tumors the prevalence of S-p53Abs significantly correlated with higher grade (p <0.01), higher stage (p = 0.02), positive lymph nodes (p = 0.03) and p53 nuclear accumulation (p <0.01). However, disease specific survival after nephroureterectomy did not differ between patients with negative and positive S-p53Abs. CONCLUSIONS: Our data suggest the possibility of the clinical application of S-p53Abs, especially for the detection of high grade or high stage tumors in the upper urinary tract. However, the usefulness of S-p53Abs as prognostic marker seems to be extremely limited in patients with urothelial tumors.