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PubMed2001

Changes of phenotypic expression of prostatic antigen in secondary transitional cell carcinoma of the prostate: evidence for induction phenomenon as a mechanism for acquisition of prostatic antigens in prostatic transitional cell carcinoma.

BACKGROUND: In vitro and experimental studies of mesenchymal-epithelial interaction for the prostatic stroma have demonstrated that the prostatic stroma is capable of inducing the nonprostatic epithelium to acquire many features of prostatic epithelium. We investigated whether this phenomenon could be observed in vivo in human prostatic stroma. MATERIALS AND METHODS Sixty transitional cell carcinoma (TCC) of the urinary bladder: (a) 20 with glandular lumen; (b) 20 without glandular lumen: (c) 10 mixed TCC-adenocarcinoma (ACA); and (d) 10 with synchronous or metachronous TCC of the prostate; and three primary TCC of the prostate were examined and submitted for immunostaining for prostatic acid phosphatase (PAP) and prostatic specific antigen (PSA). RESULTS: There was a spectrum of immunostaining for PSA ranging from negative reactivity in TCC without glandular lumen of the urinary bladder, to focal and weak reactivity in single cells with varying degrees of nonmucinous glandular differentiation and to strong reactivity in groups of cells in primary and synchronous or metachronous TCC in the prostate. The areas of carcinoma geographically closest to the prostate and with the most extensive nonmucinous glandular differentiation displayed the most frequent and strongest immunoreactivity for PSA. The immunoreactivity for PAP was usually stronger than for PSA. Four cases of TCC and mixed TCC-ACA were immunoreactive only for PAP. Furthermore, there was a change in the phenotype of TCC in the urinary bladder as it spread into the prostate. For 10 TCC in the urinary bladder with synchronous or metachronous tumor in the prostate, all TCC in the urinary bladder were negative for PAP and PSA, whereas six TCC in the prostate were focally positive. CONCLUSIONS: The spectrum of immunoreactivity for PAP and PSA and the change in immunoreactivity of TCC of the urinary bladder as it spreads into the prostate are likely induced by the prostatic stroma through the mechanism of mesenchymal-epithelial interaction. Prostate 47:172-182, 2001.

Acid Phosphatase↗
PubMed1987

Detection of onco-fetal bladder antigen in urine of patients with transitional cell carcinoma.

Studies of antigens associated with transitional cell carcinoma were extended by using murine IgM monoclonal antibody E7, developed earlier by this laboratory. These antibodies react preferentially with human bladder tumors and transitional cell carcinoma (TCC) cell line 647V. We now report that monoclonal antibody E7 detected the presence of antigen in midgestational and third trimester amniotic fluids, and in urine of patients with advanced transitional cell carcinoma. Western blot analysis showed that the antigen present in amniotic fluids consists of a sharp band with molecular weight greater than 200 kdaltons. A similar molecular weight pattern was seen with the solubilized membrane of 647V. A sensitive and convenient sandwich ELISA was developed and the urine of patients with bladder cancer was assayed for the presence of the E7 antigen. Antigen was detected in the urine of patients with advanced transitional cell carcinoma but not in the urine of normal adults or in urine from patients with prostate cancer, renal cell carcinoma, or benign prostate hyperplasia. An inhibition enzyme immunoassay was developed with monomeric forms of the E7 antibody and confirmed the presence of antigen in the urine of patients with TCC. We conclude that the E7 antigen is an onco-fetal antigen expressed in patients with transitional cell carcinoma of the bladder.

Antibodies, Monoclonal↗
PubMed2000

Concomitment spread of a renal cell carcinoma beyond the kidney and a transitional cell carcinoma beyond the bladder.

We report the case of a 61-year-old man, with a rare combination of two advanced urological tumors: a concomitant spread of an adenocarcinoma beyond the kidney and a urothelial carcinoma beyond the bladder. We simultaneously performed a primary curative prostatovesiculectomy and a nephroureterectomy on the right with ileal neobladder. To our knowledge, a case report of concomitant spread of an adenocarcinoma beyond the kidney (pT3 pN0 M0 G3) and a urothelial carcinoma beyond the bladder (pT3a pN0 M0 G3) with subsequent curative therapy has thus far not been published. A combination of the two diseases described here is obviously a remarkable rarity.

Carcinoma, Renal Cell↗
PubMed1998

Loss of CD44 variant 6 expression differentiates small cell carcinoma of urinary bladder from urothelial (transitional cell) carcinoma.

AIMS: Small cell carcinoma of the urinary bladder has a more aggressive biological potential than urothelial carcinoma, but its morphology may overlap with poorly differentiated urothelial carcinoma. The CD44 family of glycoproteins mediates cell-cell and cell-matrix adhesion. Aberrant regulation of expression of CD44, and particularly its v6 variant exon, has been correlated with aggressive or metastatic phenotype of some cancers. We measured the degree of protein expression of CD44v6 in small cell and urothelial bladder carcinoma. METHOD AND RESULTS: Immunohistochemical staining was performed with monoclonal antibodies against CD44v6. Immunoreactivity was absent in 25 of 27 cases of small cell carcinoma, with two showing only weak staining of fewer than 10% of cells. In contrast, all 12 cases of moderately or poorly differentiated urothelial carcinoma displayed moderately intense reactivity in 50% to 100% of cells. CONCLUSIONS: CD44v6 immunostaining discriminates cases of poorly differentiated urothelial carcinoma from small cell carcinoma. It also highlights the presence of mixed small cell urothelial differentiation when present.

Aged↗
PubMed1982

The clonogenic growth of cells derived from bladder barbotage in patients with transitional cell carcinoma of the bladder: a preliminary report.

Tumor cells obtained from bladder washings in 41 patients with transitional cell carcinoma of the bladder and 15 control subjects were analyzed for their ability to produce cluster and/or colony formation in a tumor stem cell assay. In vitro cell growth was correlated with the presence of tumor at the time of bladder washing, tumor grade and treatment status. Of 34 bladder washings from patients with biopsy-proved transitional cell carcinoma 88 per cent produced cluster and/or colony formation. Specimens from patients not currently receiving intravesical chemotherapy at the time of bladder barbotage produced colonies in 54 per cent of the cases, compared to 25 per cent from patients receiving therapeutic or maintenance therapy. Higher grade tumors produced more viable cells at bladder barbotage but clonal growth rates were independent of histologic grade. We conclude that bladder barbotage may serve as a source of cells for chemotherapeutic drug testing in patients with transitional cell carcinoma of the bladder. Bladder washings also may be useful as a source of tumor cells for monitoring the in vivo growth potential of bladder cancer in the tumor stem cell assay.

Carcinoma, Transitional Cell↗
PubMed1993

Transitional cell carcinoma of the renal pelvis with choriocarcinomatous differentiation. Immunohistochemical and immunoelectron microscopic assessment of human chorionic gonadotropin production by transitional cell carcinoma of the urinary bladder.

BACKGROUND: There have been 12 documented cases of choriocarcinoma arising in the urinary bladder, either alone or in combination with other epithelial tumors. It has been shown that some high-grade transitional cell carcinomas (TCC), without obvious syncytiotrophoblastic elements, can produce human chorionic gonadotrophins (HCG). METHODS: A case of choriocarcinoma, in association with high-grade TCC of the renal pelvis, was encountered in an 80-year-old man. For additional evaluation of HCG production by TCC, 25 consecutive cases of invasive high-grade TCC of the bladder were stained with an anti-HCG antibody. Immunogold staining also was performed in two of the cases studied. RESULTS: Immunoperoxidase staining of the renal pelvis tumor showed focal positivity for HCG within the TCC and a more intense reaction as the tumor cells differentiated into choriocarcinoma elements. Seven of the 25 cases (28%) displayed varying degrees of reactivity within individual cells or groups of cells. In an additional case, typical syncytiotrophoblastic giant cells without cytotrophoblasts were seen in a high-grade TCC. Immunogold studies demonstrated positive labeling in the cytoplasm of carcinoma cells in a case of TCC without syncytiotrophoblasts and in the syncytiotrophoblastic giant cells in the one case in which these were present. CONCLUSIONS: The findings support a metaplastic origin of cases of choriocarcinoma arising primarily in the urothelial tract.

Aged↗
PubMed1980

[Immunologic determination of an epidermal G2-chalone-like factor as a marker of squamous cell structures in the urinary bladder and urine in rats].

The epidermal G2 chalone-like substance of the rat skin may be determined by immunochemical methods only in squamous epithelia and it is revealed neither in mucosa of the urinary bladder, nor in urine of control rats. The antigenic activity of the chalone was revealed in 37 extracts of 56 tumors of the rat bladder. All antigen-containing tumors were found to be squamous cell carcinomas, transitional cell carcinomas with squamous cell metaplasia or possessed ultramicroscopic signs of squamous cell metaplasia appearing as "pure" transitional cell carcinomas under light microscope. The epidermal G2 chalone-like substance was present in urine of 7 out of 10 rats bearing the antigen-positive tumors of the urinary bladder.

Animals↗
PubMed1990

Transitional cell carcinoma of the urinary bladder with osteoclast-type giant cells: a report of two cases and review of the literature.

We report two transitional cell carcinomas of the urinary bladder containing numerous osteoclast-type giant cells that stained for vimentin and acid phosphatase (with and without tartrate) and were negative for cytokeratin and lysozyme. One tumour, in a 65-year-old man, was composed of papillary transitional cell carcinoma, invasive poorly differentiated carcinoma with a prominent spindle cell component and numerous osteoclast-type giant cells; repeat curettage 2 months later showed no residual tumour. The second tumour occurred in a 75-year-old woman who underwent a radical cystectomy for a deeply invasive transitional cell carcinoma with a spindle and anaplastic giant cell component and areas containing numerous osteoclast-type giant cells. Osteoclast-type giant cells, which appear to be reactive, should be distinguished from the neoplastic giant cells of giant cell carcinoma.

Acid Phosphatase↗
PubMed2005

[Is there a place for randomized biopsies in the follow up of superficial transitional cell carcinoma of the urinary bladder?].

INTRODUCTION: Transitional cell carcinoma of the bladder represents a disease of entire urothelial tract. The follow up is very important to detect any lesion that might represent a progression or a local recurrence. Some authors recommend randomized biopsies as a routine workup, others recommend cystoscopies and urinary cytology as the main part of superficial bladder cancer follow up. PATIENTS AND METHODS: Forty nine patients with superficial bladder cancer were followed up during a ten-year period. Randomized biopsies and urinary cytology were harvested according to the international cancer protocol on bladder cancer. RESULTS: 15 (1%) out of 1.489 randomized biopsies found to be positive to transitional cell carcinoma. Four out (10.5%) of 35 biopsies targeted to suspicious areas were positive to transitional cell carcinoma. 50 (17.4%) out of 288 cystoscopies with urinary cytology found to be positive to transitional cell carcinoma. Sensitivity and Specificity of biopsies (including randomized and targeted) were 31% and 85.2% respectively. Sensitivity and specificity of cystoscopies with urinary cytology were 48% and 86.5% respectively. CONCLUSION: Randomized biopsies did not show to detect more local recurrence or progression when compared to the urinary cytology. Cystoscopies with urinary cytology have good sensitivity and specificity for detection of tumor recurrence during follow up of transitional cell carcinoma.

Adult↗
PubMed1994

PCNA/cyclin expression in transitional cell carcinomas of the human bladder: its correlation with Ki-67 and epidermal growth factor receptor immunostainings.

Cell kinetic data are an important adjunct to histologically based tumor classifications and provide reliable information about future tumor behaviour. The growth fraction of 62 transitional cell carcinomas was assessed using Ki-67 and PCNA (Proliferating cell nuclear antigen/cyclin) immunostainings. Ki-67 recognises an unknown nuclear antigen expressed in dividing cells and requires the use of frozen sections. PCNA, a non histone nuclear protein, identifies proliferating cells within fixed, embedded tissue sections. The percentage of labeled cells was expressed as the labeling index (LI). The median LI in normal urothelium and transitional cell carcinoma were 0.5% and 8%, respectively for Ki-67, and 1.5% and 12% for PCNA. A general agreement between indices of cell proliferation and histological grade and stage was demonstrated. Although some discrepancies were observed, there was a strong correlation between Ki-67 and PCNA Lis (r = 0.8308, P < 0.01). In addition, tumor EGFR positive had PCNA values greater than those found in cancer EGFR negative (P = 0.01). These findings suggest that immunohistochemical nuclear labeling with anti-PCNA on routinely processed tissue is a simple technique for the assessment of transitional cell carcinomas.

Adult↗
PubMed1980

Characterization of cell-mediated cytolytic mechanisms against human transitional cell carcinoma line, 253J.

We examined the nature of effector cells that mediate antibody-dependent cell-mediated cytotoxicity (ADCC) and spontaneous cell-mediated cytotoxicity (SCMC) against the 253J human bladder transitional cell carcinoma cell line. Fractionation of peripheral blood lymphocytes (PBL) showed that ADCC and SCMC against the 253J targets were mediated by non-adherent, surface immunoglobulin-negative lymphocytes lacking or having only weak affinity for sheep erythrocytes. Macrophages were not cytotoxic against 253J cells in 18 h culture, as removal of macrophages by glass adherence or treatment with silica particles did not reduce ADCC or SCMC, and macrophage-enriched effector cell preparations were only weakly cytotoxic.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1990

Transitional cell carcinoma of bladder in children.

Transitional cell carcinoma of the bladder occurs rarely during the first two decades of life. The malignancy is usually low grade and noninvasive, with a low recurrence rate. Transurethral resection or fulguration is the treatment of choice, and the prognosis is favorable. We present 4 patients, aged two to eighteen years, with transitional cell carcinoma of the bladder and review the literature.

Adolescent↗
PubMed1977

A cell line from an anaplastic transitional cell carcinoma of human urinary bladder.

A cell line, TCCSUP, derived from an undifferentiated, Grade IV transitional cell carcinoma is described. The karyotype showed an abnormal distribution of chromosomes, with no obvious modal number. Distinct marker chromosomes were observed in both early and late in vitro passages. These cells have been subcultured over 50 times during a 20-month period. TCCSUP differs in certain morphological and immunological features from other cell lines from transitional cell carcinomas.

Carcinoma, Transitional Cell↗
PubMed1994

Two molecular pathways to transitional cell carcinoma of the bladder.

Noninvasive transitional cell carcinomas of the bladder can have two distinct morphologies suggesting they contain different genetic alterations. Papillary transitional cell carcinomas (T(a) tumors) are often multifocal and only occasionally progress, whereas flat tumors (carcinomas in situ, CIS), frequently progress to invasive disease. We examined 216 bladder tumors of various stages and histopathologies for two genetic alterations previously described to be of importance in bladder tumorigenesis. Loss of heterozygosity of chromosome 9 was observed in 24 of 70 (34%) T(a) tumors but was present in only 3 of 24 (12%) CIS and dysplasia lesions (P = 0.04). In contrast, only 1 of 36 (3%) T(a) tumors contained a p53 gene mutation compared to 15 of 23 (65%) CIS and dysplasias (P < 0.001), a frequency comparable to that observed in muscle invasive tumors (25 of 49; 51%). The presence of p53 mutations in CIS and dysplasia could explain their propensities to progress since these mutations are known to destabilize the genome. Analysis of several tumor pairs involving a CIS and an invasive cancer provided evidence that the chromosome 9 alteration may in some cases be involved in the progression of CIS to more invasive tumors, in addition to its role in the initiation of T(a) tumors. However, the CIS and secondary tumor were found to contain different genetic alterations in some patients suggesting divergent progression pathways. Bladder carcinogenesis may therefore proceed through two distinct genetic alteration pathways responsible for generating superficial tumors with differing morphologies and pathologies.

Alleles↗
PubMed2005

BCG directly induces cell cycle arrest in human transitional carcinoma cell lines as a consequence of integrin cross-linking.

BACKGROUND: Current models of the mechanism by which intravesical BCG induces an anti-tumor effect in urothelial carcinoma propose a secondary cellular immune response as principally responsible. Our group has demonstrated that BCG mediated cross-linking of alpha51 integrin receptors present on the tumor surface elicits a complex biologic response involving AP1 and NF-kappaB signaling as well as the transactivation of immediate early genes. This study evaluated the direct biologic effect of cross-linking alpha5beta1 integrin on cell cycle progression and apoptosis in two human urothelial carcinoma cell lines. METHODS: Two independent assays (MTT and Colony forming ability) were employed to measure the effect of alpha5beta1 cross-linking (antibody mediated or BCG) on cellular proliferation. Flow cytometry was employed to measure effect of BCG and alpha5beta1 antibody mediated cross-linking on cell cycle progression. Apoptosis was measured using assays for both DNA laddering and Caspase 3 activation. RESULTS: Results demonstrate that integrin cross-linking by BCG, or antibody mediated crosslinking of alpha5beta1 resulted in a decrease in proliferating cell number. BCG treatment or alpha5beta1 cross-linking increased the percentage of cells in G0/G1, in both 253J and T24 cell lines. Peptide mediated blockade of integrin binding site using RGDS reversed the effect BCG on both proliferation and cell cycle arrest. Apoptosis in response to BCG was not identified by either DNA laddering or Caspase 3 activation. CONCLUSION: These findings show that BCG exerts a direct cytostatic effect on human urothelial carcinoma cell lines. Cell cycle arrest at the G1/S interface is a mechanism by which BCG inhibits cellular proliferation. This effect is duplicated by antibody mediated cross-linking of alpha5beta1 and likely occurs as a consequence of crosslink-initiated signal transduction to cell cycle regulatory genes.

Adjuvants, Immunologic↗
PubMed2002

Prognostic impact of extensive parenchymal invasion pattern in pT3 renal pelvic transitional cell carcinoma.

BACKGROUND: Pathologic T3 renal pelvic transitional cell carcinoma exhibits various patterns of invasion. The authors investigated the prognostic impact of three patterns of invasion of pT3 renal pelvic transitional cell carcinoma. METHODS: Of 212 patients who underwent surgery for renal pelvic transitional cell carcinoma, 70 with pT3 disease were eligible for the main analyses. The candidate predictors of prognosis included patient age, gender, lesion laterality, tumor grade, perioperative cisplatin-based systemic chemotherapy, lymph node involvement, vascular involvement, and patterns of invasion. Invasion patterns were classified as fat invasion, ductal involvement, or parenchymal invasion. RESULTS: Mean postoperative followup was 33.5 months (range, 1-136 months). On univariate analysis, gender, lymph node involvement, vascular involvement, and extensive parenchymal invasion each had a significant impact on the cause specific survival rate. A multivariate analysis using Cox stepwise regression revealed that extensive parenchymal involvement was the strongest prognostic predictor (P = 0.0004, hazard ratio = 5.59). Lymph node involvement (P = 0.0175, hazard ratio = 3.14) and gender (P = 0.0361, hazard ratio = 2.42) were other weaker predictors. Statistically, pT3 disease without extensive parenchymal invasion had a prognosis similar to that of lower stage disease, and pT3 disease with extensive parenchymal invasion had a prognosis similar to that of pT4 disease. CONCLUSIONS: Extensive parenchymal invasion has a strong prognostic impact in renal pelvic transitional cell carcinoma. pT3 disease should be subclassified into two separate entities, that with and that without extensive parenchymal invasion, in view of prognosis.

Adult↗
PubMed1996

Annular constriction of the rectum secondary to transitional cell carcinoma of the bladder.

Recurrent transitional cell carcinoma of the bladder is often a locally progressive disease. Regional lymph node metastasis is a frequent finding and may be the first sign of recurrence. Involvement of the gastrointestinal tract is rare, but metastasis to the colon, small intestine, and stomach have been reported. Herein, we present a case of recurrent transitional cell carcinoma of the bladder manifesting as an annular constricting mass of the rectum, and review the literature regarding this unusual lesion.

Aged↗