Metatarsal metastasis from transitional cell cancer of the urinary bladder

Urinary bladder cancers can be grouped into three general categories: superficial, invasive and metastatic. Approximately 90% of malignant tumors of the urinary bladder are of epithelial origin and the majority of them are transitional cell carcinomas (TCC). Metastatic spread of urinary bladder cancers usually includes regional lymph nodes, the lung, the liver and the bones. The presence of metastasis tends to correlate with muscular wall invasion as often demonstrated at the initial diagnosis; consequently clinical bladder cancer represents a late phase of the disease. Although skeletal metastases of bladder cancers are rather common, they have been rarely described to occur in distal bones. For that reason, we report metatarsal metastasis from transitional cell cancer of the urinary bladder in a 59-year-old woman.     

Proteome-based diagnostics and prognosis of bladder transitional cell carcinoma

More than 90% of bladder tumors are diagnosed as bladder transitional cell carcinoma and the majority of these lesions (70%) are diagnosed as superficial papillary lesions (stage pTa, T1). Recurrences are common to superficial tumors and few lesions will progress to a higher grade and/or stage and muscle invasion. Thus, diagnosing cancer at an early stage, predicting whether a tumor will recur and/or progress and identification of novel targets for cancer intervention, become the main focus of bladder cancer research. The purpose of this article is to briefly review what has been accomplished to date by using proteomic technology in order to develop a new strategy to resolve the problems of early detection, recurrence or therapeutic intervention.     

Chromosomal and cell kinetic pattern in human transitional cell bladder carcinoma

Cell kinetics in transitional cancer of the bladder was studied in 35 patients by using the in vitro 3H-thymidine labeling index. The proliferative activity was remarkably lower than that observed for other human histotypes. Analysis of the relation between cell kinetics and histologic grading showed a value for grade III tumors two-fold that of grade I and grade II tumors. Cytogenetic analysis was possible in 15 cases, and different chromosome numbers from 40 to 120 and the presence of various structural aberrations were observed. When cytogenetic features were analyzed in relation to cell kinetics, higher proliferative activities were always associated with a loss of chromosome 13 and, except for one case, with a loss of chromosome 22.     

Immunocytochemistry of collagenase expression in transitional cell carcinoma of the bladder

OBJECTIVE: To evaluate the usefulness of collagenase immunocytochemistry as well as its immunohistochemistry in assessing the correlation with prognostic factors in transitional cell carcinoma (TCC) of the urinary bladder. STUDY DESIGN: We investigated the expression of collagenase in catheterized urine and histologic specimens from 38 patients with TCC and 20 cases with benign lesions of the urinary tract. RESULTS: Thirteen (34.2%) and 17 (44.7%) patients with TCC showed positive expression of collagenase on cytologic and histologic specimens, respectively, whereas in no cases with benign lesions was such expression found (P < .01). Invasive and nonpapillary TCC had higher positive rates than noninvasive and papillary TCC. Grade 3 TCC was positive at a higher rate than was grade 2, whereas there were no positive cases with grade 1. Collagenase expression did not correlate significantly with stage. CONCLUSION: Collagenase expression in urinary TCC correlated well with tumor growth pattern, pathologic grade and invasiveness of the carcinoma; all are known to be prognostic factors. The application of collagenase immunostaining to urinary cytology is very useful for assessing prognosis in TCC.     

Subcutaneous metastasis from transitional cell carcinoma of the bladder diagnosed by fine needle aspiration biopsy. A case report

BACKGROUND: Metastasis of transitional cell carcinoma (TCC) of the bladder to the skin and subcutaneous tissue is an uncommon finding. CASE: A 58-year-old man with a known case of high grade TCC of the bladder, presented with a right paraspinal mass. Clinically an abscess was suspected. Fine needle aspiration (FNA) showed many clusters and isolated malignant cells in an inflammatory background. The smears were diagnosed as positive for malignancy. CONCLUSION: It is essential to differentiate tumors metastatic to the skin and subcutaneous tissue from inflammatory lesions. FNA helped with the diagnosis in this case and prevented unnecessary biopsy.     

Metastatic transitional cell carcinoma of the urinary bladder to the shoulder girdle

Transitional cell carcinoma (TCC) of the bladder typically metastasizes to the pelvic lymph nodes and to visceral sites including the lungs, liver, and bones. Other sites include the brain, especially after systemic chemotherapy. To our knowledge, we report the first case of TCC metastatic to the soft tissue of the shoulder girdle and discuss common and unusual sites of metastasis in TCC.     

Adjuvant Bestatin immunotherapy in patients with transitional cell carcinoma of the bladder

Summary The first clinical results of an ongoing, prospective trial to determine the value of adjuvant Bestatin immunotherapy in the management of bladder cancer are presented. Patients with nonmetastatic transitional cell carcinoma of the bladder, scheduled for fulldose local radiation therapy (64 Gy), were randomly allocated to adjuvant oral Bestatin treatment (30 mg daily for at least 1 year), starting at completion of irradiation, or no Bestatin. The longest follow-up period of the 151 evaluable patients is 6 years. The results have shown that the disease-free survival of the patients taking Bestatin is significantly improved compared to the controls (p=0.04). However, the overall survival of the patients was not affected by the Bestatin treatment. The beneficial effect of Bestatin seemed to be more marked among men than women. Furthermore, statistical analyses of the patient material according to T tumor categories suggested that compared to the controls, patients with less advanced disease (T1 and T2) benefitted more from Bestatin treatment than those with more advanced tumors (T3 and T4). The results of this ongoing trial thus show that patients with bladder cancer benefit from adjuvant Bestatin treatment in terms of disease-free survival.     

Spontaneous cell-mediated cytotoxicity in patients with transitional cell carcinoma of the urinary bladder

Summary Lymphocytes isolated from the blood of TCC patients, like those of control patients, were capable of mediating spontaneous cell-mediated cytotoxicity against K-562 cells. When this natural cytotoxicity was analyzed with regard to the effector cell type it was found that in TCC patients the SLMC was mostly displayed by E-rosetting T lymphocytes, whereas compared with controls, a significant decline in the SLMC of the non-T lymphocytes was observed. The SLMC of the T lymphocytes derived from TCC patients was further demonstrated on a T leukemia target cell (Peer). When the SLMC on K-562 and on Peer target cells was compared, a specificity difference was observed between TCC and the control patients' effector cells. The SLMC activity of the TCC patients' T cells was not abolished after depletion of Fc receptor-positive cells or following treatment with monoclonal antibodies OKT 8 or OKT 4 and complement (C'). These NK-like cells are therefore distinguished from cytotoxic T lymphocytes and NK cells.     

Co-localization of GSTP1 and JNK in transitional cell carcinoma of urinary bladder

Transitional cell carcinoma (TCC) of urinary bladder belongs to glutathione S-transferase P1 (GSTP1) overexpressing tumors. Upregulated GSTP1 in TCC is related to apoptosis inhibition. This antiapoptotic effects of GSTP1 might be mediated through protein:protein interaction with c-Jun NH(2) -terminal kinase (JNK). Herein, we analyzed whether a direct link between GSTP1 and JNK exists in TCC. The presence of GSTP1/JNK complexes was analyzed by immunoprecipitation and Western blotting in 20 TCC specimens, obtained after surgery. Co-localization of GSTP1 and JNK was also investigated in the 5637 TCC cell line by immunofluorescence confocal microscopy. By means of immunoprecipitation we show for the first time the presence of GSTP1/JNK complexes in all TCC samples studied. A co-localization of GSTP1 and JNK was also demonstrated in the 5637 TCC cell line by means of confocal microscopy. Protein-protein interactions, together with co-localization between GSTP1 and JNK provide evidence that GSTP1 most probably inhibits apoptosis in TCC cells by non-covalent binding to JNK.     

A comparative study in morphometric grading of transitional cell carcinoma of the urinary bladder

To overcome the considerable observer inconsistency in the histologic grading of transitional cell carcinomas, the value of four different morphometric grading methods was investigated in 61 tumors of the bladder. Only two methods showed satisfactory reproducibility. Both methods, one based on random nuclear sampling and the other on selective nuclear sampling, showed an increase in the mean and standard deviation of the nuclear area with higher tumor grades (P less than .00001). Morphometric classification of the learning set (44 cases) was in agreement with the unequivocally assessed histologic grade in 35 cases (79.5%) using random sampling and in 38 cases (86.4%) using selective sampling. By reducing the grading classes to "low" (grades 1 and 2) and "high" (grade 3) and by introducing a classification probability threshold (0.80), an accurate morphometric classification was achieved in 38 cases (86.4%) using random sampling and in 41 cases (93.2%) using selective sampling. Of the 17 cases with histologic grading discrepancies, all 10 low-grade tumors (with discrepancies of grade 1 versus grade 2) were correctly classified as low-grade carcinomas by both of the morphometric methods; in the remaining 7 cases, with low-versus-high discrepancies (grade 2 versus grade 3), the selective method yielded better correlation with the tumor stage and clinical follow-up. It is concluded that morphometric classification is an acceptable alternative for histologic grading by pathologists, provided that the reproducibility of the method is confirmed. Although both random and selective sampling yielded satisfactory classifications, the selective method gave more reliable results as confirmed by the clinical behavior.     

Monoclonal antibodies to antigens associated with transitional cell carcinoma of the human urinary bladder

Summary Spleen cells from BALB/c mice immunized with cells derived from transitional cell carcinomas (TCC) of the human urinary bladder were fused with mouse myeloma Sp 2/0 Ag14 cells. Monoclonal antibodies from six established hybridomas were investigated for specificity in a cell ELISA and in indirect immunofluorescence against a large panel of fixed intact cells. Three of the antibodies reacted with half or more of the eight bladder tumors and with a few unrelated tumors. They did not react at all with malignant or normal cells of hematopoietic origin. A fourth antibody reacted with seven of eight bladder tumors. It also reacted weakly with a prostatic carcinoma, with five of six malignant or transformed B cell lines, and with a subpopulation of normal lymphocytes, but not with any of the other cells on the test panel. These four antibodies did not react with cells derived from normal urothelium. The results suggest that these antibodies might recognize cell-type-restricted antigens associated with malignancy. Another antibody reacted with almost all urothelium-derived cells. It also reacted with three of three melanomas but not with any other cells on the panel. The sixth antibody reacted with 32 of the 37 cells tested. The spectrum of reactivities displayed by the antibody suggested that it recognizes HLA antigens. Abbreviations used in this paper: TCC, transitional cell carcinoma of the urinary bladder; TAA, tumor-associated antigens; ELISA, enzyme-linked immunosorbent assay; NBCS, newborn calf serum; PBS, phosphate-buffered saline, pH 7.2; ALP, alkaline phosphatase; GDA, glutardialdehyde; BSA, bovine serum albumin; IF, indirect immunofluorescence; LCL, lymphoblastoid cell lines: B-lymphocytes transformed in vitro with Epstein-Barr virus     

Cytologic evaluation of low grade transitional cell carcinoma and instrument artifact in bladder washings

OBJECTIVE: To identify key cytologic features for the separation of low grade transitional cell carcinomas (TCCs) from nonneoplastic lesions in bladder washings. STUDY DESIGN: The cytomorphologic features of 95 bladder washing specimens showing papillary fragments, which included 50 low grade TCCs and 45 nonneoplastic lesions, were reviewed retrospectively. RESULTS: Bladder washings from low grade TCCs showed papillary and irregular groups of cells with ragged borders, cytoplasmic homogeneity and subtle nuclear changes, such as increased nuclear/cytoplasmic ratio and irregular nuclear border. Bladder washings after instrumentation from nonneoplastic lesions of the bladder showed cellular specimens with cohesive, ball-shaped and papillary clusters with smooth borders lined with a denser-staining cytoplasmic collar. Reactive urothelial cells often displayed loose aggregates with irregular borders but no cytoplasmic collar. CONCLUSION: In bladder washing cytology, nuclear changes and cytoplasmic homogeneity play a major role in the diagnosis of carcinoma.     

Molecular pathology of low malignant bladder transitional cell carcinoma: a current perspective

Bladder transitional cell carcinoma (BTCC) actually has two phenotypes: low malignant and aggressive. Most previous molecular and cytogenetic analyses of bladder cancer were focused on aggressive BTCC. Little is known about the events that lead to the development of low malignant BTCC. This review mainly introduces the concept of two types of bladder tumors and then focuses on the molecular pathology of low malignant BTCC in particular. It is hoped that further understanding of the molecular pathology of low malignant BTCC may provide novel therapies and many other clinical benefits in patients with this disease.     

Quantitative microscopy of human DNA topoisomerase II-alpha expression in transitional cell carcinoma of the bladder

OBJECTIVE: To compare the nuclear size of various grades of transitional cell carcinoma (TCC) stained immunohistochemically with the nuclear enzyme topoisomerase II-alpha (topo II-alpha) in bladder urothelial neoplasms. STUDY DESIGN: Histologic sections from 53 consecutive papillary bladder neoplasms were stained immunohistochemically for topo II-alpha expression. There were 18 (33.9%) urothelial neoplasms of low malignant potential (UNLMP), 18 (33.9%) low grade urothelial carcinoma (LGUCa), and 17 (32%) with high grade urothelial carcinoma (HGUCa). The histologic slides were photographed at 400 x magnification and then projected on a screen, and the area with stained nuclei was measured. RESULTS: The cells and nuclei in HGUCa were significantly larger than in LGUCa (P < .05) and UNLMP (P < .01). CONCLUSION: Calculation of the area fraction of nuclei in TCC of the bladder stained with topo II-alpha is an additional method of establishing the grade of these tumors.     

Clinical relevance of serum angiogenic activity in patients with transitional cell carcinoma of the bladder

Angiogenesis is essential for tumor growth and progression and is mediated by positive and negative regulators of vessel growth. Since angiogenic mediators found in patient serum have been postulated to reflect the angiogenic potential of a malignant tumor, we investigated the angiogenic activity in the serum of patients with transitional cell carcinoma (TCC). The data were correlated to tumor characteristics and the clinical course of the patients. Eighty-one patients with transitional cell carcinoma and 53 control persons were included in the study. Preoperative serum samples were collected and both vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were quantified by ELISA. Additionally, the serum evoked proliferative activity on human umbilical vein endothelial cells (HUVEC) was evaluated. Data were compared to the clinical course of the patients. Serum of tumor patients significantly enhanced the proliferative capacity of HUVEC, compared to cells grown in standard culture medium (p = 0.0032), but not when compared to serum from control persons. Serum from patients with superficial TCC and well differentiated tumors induced a significantly higher angiogenic response (ANG(hi)) than serum from patients with poorly differentiated and invasive carcinomas (ANG(lo); p = 0.037). VEGF level of ANG(hi) serum was 384.22 +/- 247.76 pg/ml (n = 37) which significantly differed from mean VEGF level detected in ANG(lo) serum (247.72 +/- 211.93 pg/ml, n = 42; p = 0.019). Similarly, mean bFGF levels were 9.58 +/- 5.91 pg/ml in ANG(hi) serum versus 5.74 +/- 3.52 pg/ml) in ANG(lo) serum (p = 0.0043). A negative correlation was established between VEGF/bFGF serum concentration and patient prognosis. The experiments demonstrate a positive correlation between VEGF and bFGF serum level and endothelial proliferation in vitro. The inverse relationship between angiogenic activity and tumor stage might disclose information about angiogenesis and tumor progression in TCC.