Expression of ABH blood group isoantigen as a prognostic factor in transitional cell bladder carcinoma

The expression of ABH blood group isoantigen was determined with the avidin-biotin-peroxidase complex method in a retrospective consecutive material of 230 patients with transitional cell bladder carcinoma. The follow-up period was 5 to 9 years. The five-year corrected survival for 65 patients whose primary tumours showed predominant expression of ABH antigens ('positive') was 80% and for 146 patients with predominant deletion ('negative') 60% (p less than 0.01). Of 107 patients with superficial tumours there were 60 negative and 47 positive. In an analysis of early progression, the negative tumours were found to progress more frequently than positive ones (p less than 0.03). Twenty-three per cent of the negative tumours finally progressed during the whole follow-up, compared with 15% of the positive ones; this difference was not significant. Almost all progressing tumours became negative when they reached an advanced stage.     

DNA ploidy as a prognostic factor in muscle invasive transitional cell carcinoma of the bladder

Radical cystectomy represents the treatment of choice for muscle-infiltrative bladder carcinoma; however, about 50% of patients relapse and die from the disease. In the present study, the prognostic significance of the DNA ploidy in transitional cell carcinoma of the urinary bladder (TCCB) is analyzed. The study was carried out on 66 patients with TCCB who underwent radical cystectomy. DNA ploidy was determined by flow cytometry (FCM) on paraffin-embedded specimens, and the results were analyzed and correlated with the tumor malignancy grade and stage and the clinical course. Forty of the 66 tumors studied (63%) were aneuploid. Aneuploid status was correlated with higher tumor T stage (P<0.001) and grade (P<0.001). Median follow up was 68 months (range: 12–105). Median survival was significantly longer in patients with diploid tumors (>60 vs 45 months, P<0.001). All patients with diploid tumors were alive and free of bladder cancer during follow-up, in contrast to only 30% of patients with aneuploid tumors. DNA ploidy was an independent prognostic factor, as shown by multivariate analysis (P=0.006). All patients with pT3b and diploid tumors were alive at the time of analysis as opposed to none with aneuploid tumors. The results of this study suggest that DNA ploidy can provide prognostic information on patients with muscle invasive carcinoma of the bladder and might represent a means of selection for postoperative management.     

Human DNA topoisomerase-IIalpha expression as a prognostic factor for transitional cell carcinoma of the urinary bladder

OBJECTIVE: To investigate the immunohistochemical expression of topoisomerase II-alpha (TII-alpha, a nuclear enzyme, the expression of which increases rapidly at the end of the S to G2/M phase and declines when mitosis ends) in bladder urothelial neoplasms (transitional cell carcinoma), and its correlation with grade, stage and survival. PATIENTS AND METHODS: Histological sections from 57 urothelial neoplasms were stained immunohistochemically for TII-alpha expression; the percentage of positive cells in the area of greatest staining was recorded as the TII-alpha index. RESULTS: TII-alpha nuclear staining was positive in all the samples except one. The mean (sd) TII-alpha index was 10.7 (5.9) in urothelial neoplasms of low malignant potential (grade 1), 15.5 (5.0) in low-grade (grade 2) and 42.1 (13.4) in high-grade urothelial carcinoma (grade 3). The mean TII-alpha index was 10.7 (5.9), 26.3 (14.8) and 44 (19) in stages pTa, pT1 and pT2, respectively. The TII-alpha index was significant for predicting death from cancer, independently of the stage or grade of the disease (P = 0.019, hazard ratio 1.1). CONCLUSIONS: A higher TII-alpha index indicates a greater probability of recurrence of disease and lower overall survival. Therefore TII-alpha expression has prognostic value in bladder carcinoma.     

Expression and prognostic value of proliferating cell nuclear antigen in transitional cell carcinoma of the urinary bladder

Forty-eight patients with transitional cell carcinima (TCC) of the bladder were investigated. Routine paraffin-embedded sections were stained with proliferating cell nuclear antigen (PCNA) monoclonal antibody in order to determine the growth fraction of the bladder tumors and to correlate this with tumor grade, stage, development of recurrence and survival rate during follow-up. PCNA positive staining was detected in 95.8% (46/48) of the tumors. The mean labeling index (LI) of superficial tumors (Ta-1,n = 28) was 12.58 ± 12.33%, and 34.55 ± 21.89% in invasive tumors (T2-4,n = 18). A similar correlation was found in association with tumor grade. The patients were followed up for a mean of 4.9 years (range 1–14 years). The mean PCNA Ll in nonrecurrent (n = 21) and simple recurrent (n = 7) superficial tumors was 11.29 ± 11.79% and 16.44 ± 14.05%, respectively, the difference not being statistically significant. To access survival, tumors with a PCNA LI above and below the median level (21%) were compared. Those patients (n = 19) with an index of > 21% (the mean of all the PCNA values) had a worse prognosis than those (n = 27) with an index of < 21%, a difference which is statistically significant. These results suggest that PCNA LI in bladder cancer may prove to be an objective and quantitative assay of biological aggressiveness and provide significant prognostic information, although it does not help the selection of patients at risk of simple recurrence in superficial tumors.     

膀胱移行细胞癌增殖细胞核抗原表达的研究

采用免疫组化ＬＳＡＢ法对４８例膀胱移行细胞癌增殖细胞核抗原（ＰＣＮＡ）进行检测，发现ＰＣＮＡ增殖指数随肿瘤分级的升高而增高，浸润生长肿瘤ＰＣＮＡ增殖指数明显高于乳头状生长者（Ｐ＜０．００１），ＰＣＮＡ高表达组（增殖指数＞５０％）预后明显差于ＰＣＮＡ低表达组（增殖指数≤５０％）。结果表明ＰＣＮＡ可作为膀胱移行细胞癌恶性程度及预后指标之一。     

Investigation of ABH antigenicity of random mucosal biopsies and transitional cell carcinoma of the urinary bladder

Blood group isoantigens can be demonstrated immunohistologically on normal bladder urothelium by means of the specific red cell adherence test. In preneoplastic and reactive changes of the urothelium as well as in carcinoma in situ, a loss of these antigens occurs. Blood group isoantigen content decreases with higher anaplasia of transitional cell carcinoma. Overt tumors without blood group isoantigens are associated with carcinoma in situ and severe dysplasia at a high percentage. These tumors are associated significantly more often with antigen-negative light-microscopically normal-appearing urothelium than antigen-positive ones do.     

Influence of blood group type on prognosis of transitional cell carcinoma of the urinary bladder

The correlation of blood group to grade, stage and tumor markers at diagnosis and to the subsequent clinical course was investigated in a consecutive retrospective series of 230 patients with primary transitional cell carcinoma of the urinary bladder. The follow-up period was 5-9 years. There were no significant differences in grade, stage or DNA ploidy between patients of blood groups A and O. However, the deletion of ABH blood group isoantigen was found more frequently in tumors from patients of blood group O. Concerning progression of superficial bladder tumors, this was found earlier among patients of blood group O, and in a multivariate analysis this emerged as an independent prognostic factor. The crude and corrected mortality was not significantly higher among patients of group O than among those of other blood groups.     

Epithelial membrane antigen as an immunohistochemical marker for transitional cell carcinoma of the urinary bladder

Epithelial membrane antigen (EMA) was immunohistochemically localized in transitional cell carcinomas of the bladder to clarify EMA staining pattern's relationship to the histological grading and staging of tumors and patient prognosis. Formalin-fixed, paraffin-embedded sections from 101 patients with bladder carcinoma were stained by the indirect immunoperoxidase method. In the lower histological grade and stage of transitional cell carcinoma, the localization of EMA was restricted to the luminal surface of the superficial cells. Membrane and cytoplasmic staining of EMA was frequently found in the intermediate and basal layers of the tumor cells, and the incidence of cytoplasmic staining increased with advancing grade and stage. Stromal staining was frequently observed in cases of higher grade and stage. In addition, these distribution patterns of EMA were well correlated with patient survival. Thus, we differentiated three types of EMA distribution: a luminal type, with very good prognosis; a cytoplasmic type, with fair prognosis; and a stromal type, with relatively poor prognosis. These findings suggest that EMA distribution in bladder cancer could be a valuable indicator for histological grading or staging in pathological diagnosis and for predicting the survival of bladder cancer patients.     

Investigation of blood group antigens and carcinoembryonic antigen in urinary bladder carcinoma

Blood group antigens and carcinoembryonic antigen (CEA) were sought in the tissues of 37 bladder tumor cases using enzyme antibody method. A correlation (p less than 0.01) was found between the extinction of ABO (H) and progressive malignant states of the tumor or invasion stage. Significant correlation (p less than 0.05) was observed between the presence of CEA and the invasion stage. The state of the T antigen, however, did not reflect the malignancy grade or invasion stage. The states of ABO (H) and CEA significantly reflected (p less than 0.05) the prognosis, as did the malignancy grade and invasion stage, while the state of the T antigen did not correlate with the prognosis. Although there was a correlation (p less than 0.01) between the extinction of ABO (H) blood group antigens and the presence of CEA, the state of T antigen did not significantly correlate with ABO (H) antigen or CEA. From what has been mentioned, the search for intratissue ABO (H) antigens and CEA is important and will provide a useful auxiliary means in diagnosing biopsy specimens.     

Plasmacytoid transitional cell carcinoma of the urinary bladder

A case of rare plasmacytoid transitional cell carcinoma of the urinary bladder in a 60-year old man is described. The presence of end-stage disease did not allow for any efficacious therapy. Immunohistochemistry showed the tumor cells to be reactive for epithelial markers and syndecan-1 (CD138).     

Use of immunohistochemically demonstrated c-erb B-2 oncoprotein expression as a prognostic factor in transitional cell carcinoma of the urinary bladder.

Formalin-fixed, paraffin-embedded specimens from 91 primary transitional cell cancers (TCC) of the urinary bladder were stained with a monoclonal antibody to c-erb B-2 oncoprotein. Twelve percent (11/91) of the TCC stained for c-erb b-2 oncoprotein, and in 4% (4/91) of cases, the expression was graded as moderate or heavy. The expression of c-erb B-2 was significantly (p = 0.072) related to the WHO grade, whereas no significant difference in its expression was found between (a) the superficial and invasive TCC and (b) between the papillary and nonpapillary TCC. One of the tumours had a verified metastasis at the time of diagnosis and it exhibited heavy expression of c-erb B-2. The expression of c-erb B-2 was significantly related to the number of nucleolar organiser regions/TCC nucleus (p = 0.003). Aneuploid TCC were more frequently associated with moderate or heavy expression of c-erb B-2 than the diploid ones. Recurrence and progression of TCC could not be significantly related to expression of c-erb B-2 oncoprotein. In survival analysis, moderate and heavy expression of c-erb B-2 were related to poor prognosis (p = 0.032) during a mean follow-up time of 14 years. In conclusion, moderate and heavy expression of c-erb B-2 oncoprotein in TCC seems to be related to more aggressive behaviour whereas low expression of this oncoprotein had no predictive value. No evidence was obtained, however, that the expression of c-erb B-2 concoprotein alone would determine the biological behaviour of TCC.     

Determination of DNA ploidy and ABH antigen reactivity in both frozen and formalin-fixed bladder tumor tissue

Summary In a prospective series of patients with transitional-cell bladder carcinomas, DNA ploidy and ABH antigen reactivity were determined in both frozen tissue and formalin-fixed paraffin blocks. ABH antigen measurement in frozen tissue was hampered by methodological problems, especially insufficient morphology, which made quantification difficult. In only 38/55 (69%) cases was the same ABH reactivity found. The knowledge of secretor status was not helpful in the interpretation of these results. In 53/59 (90%) cases the same DNA ploidy was achieved, resulting in good correlation between flow cytometric DNA measurements in formalin-fixed and frozen tissue. The deviations occurred mainly in cases exhibiting a tetraploid DNA profile. DNA assessments using image cytometry on imprints of fresh tissue was a rapid and reliable method in our hands, with identical results being obtained in 32/36 (89%) cases.     

The prognostic relevance of nuclear Feulgen DNA in transitional cell carcinoma of the urinary bladder. A long-term follow-up study

Feulgen DNA cytophotometry yielded prognostically significant information about the long-term relative survival in 123 patients with bladder cancer, even if subgroups with comparable T categories were compared. Patients with diploid tumours generally had a more favourable outcome than those with non-diploid ones. The percentage of tumour DNA stemline values was an additional prognostic parameter for diploid T1 tumours. It is suggested that DNA cytometric results ought to have an influence on the treatment of patients with bladder cancer.     

Correlation of ABH antigenicity and urine cytology results in transitional cell carcinoma of bladder

Loss of ABH antigens from the cell surface of transitional cell carcinoma of the bladder has been proposed as an indicator of increased cellular dedifferentiation and the tendency toward invasive recurrence. An attempt was made to correlate the urinary cytology and the ABH antigen status of 57 patients with histologically confirmed bladder tumors and 28 with only dysplasia on biopsy. A review of the results of surface antigenicity studies and the preoperative urine cytologies showed no significant difference in the diagnostic sensitivity of cytology between comparable antigen negative and positive groups.     

Metastases from transitional cell carcinoma of urinary bladder

In 107 patients who died of metastatic transitional cell carcinoma, the most common sites for metastases at necropsy were the lymph nodes, liver, lung, bone, and adrenal gland. Metastases first were documented clinically in multiple-organ sites in one third of the patients; solitary metastases were present in only 9 patients at necropsy. The mean duration of survival for patients was thirteen months from the diagnosis of the primary tumor. The metastatic lesion(s) generally were evident clinically within eleven months of the primary diagnosis; death ensued usually within three months. Our finding that the majority of patients presented initially with highgrade tumors suggests that a high-grade lesion, regardless of its clinical stage, warrants early aggressive therapy.     

K-Ras mutation in transitional cell carcinoma of urinary bladder

In the present study it was aimed to investigate the frequency of K-RAS mutation in the human bladder transitional cell carcinoma. For thispurpose, tissue specimens obtained from the patients with bladder tumors.Genomic DNAs were isolated and then PCR-SSCP analysis of K-RAS genewere performed. A heterozygous deleted mutation was detected in K-RAS oncogene (exon 2) in agorose gel electrophoresis in one patient andpoint or substitution mutations are detected using single strandconformational polymorphism (SSCP) in other different patients withbladder cancer (4/14). In conclusion, the frequency of K-RAS mutationis not rare and the role of this mutation in oncogenesis and in infiltrationof the urinary bladder wall needs to be confirmed in a larger study.