Genetic defects in CHEK2 and TP53 have been implicated in prostate cancer development. However, the interaction of these two genes in prostate cancer tumorigenesis has not been investigated. We previously described 11 CHEK2 mutations in a group of 84 primary prostate tumors. In this report, we screened the same group of tumors for TP53 mutations and revealed nine somatic and two germline mutations. One germline TP53 mutation (c.408A > T/p.Gln136His) and two somatic mutations (c.1022T > G/p.Phe341Cys and c.108-109ins22/p.His37fsX13) are novel to human cancer. More interestingly, CHEK2 and TP53 mutations were observed to be mutually substituted in these tumors. Analysis of five commonly used prostate cancer cell lines revealed that four cell lines harboring TP53 mutations carry no CHEK2 mutation while the only cell line (LNCaP) carrying wild-type TP53 harbors a CHEK2 mutation. The novel CHEK2 mutation (c.1160C>T/p.Thr387Asn) identified in LNCaP cells changes amino acid Thr387 to Asn which has been shown to impair CHEK2 autophosphorylation and activation. Our data suggest that the CHEK2 and TP53 mutations can substitute each other in at least 25% (21/84) of prostate cancers and that DNA damage-signaling pathway plays an important role in prostate cancer tumorigenesis.

PURPOSE: We analyzed the expression of genes to identify reliable molecular markers in the diagnosis and progression of prostate cancer. EXPERIMENTAL DESIGN: Gene expression profiling was done using HG-U133 set microarrays in 32 prostate cancer and 8 benign tissues of patients with cancer. Expression levels of 11 genes were selected for quantitative real-time PCR evaluation in 52 prostate cancer and 20 benign tissues. Further, to assess transcriptional inactivation, we analyzed the promoter methylation of genes by quantitative methylation-specific PCR in 62 tumor and 36 benign tissues. RESULTS: Our results showed a significant down-regulation in the mRNA expression levels of PRIMA1, TU3A, PDLIM4, FLJ14084, SVIL, SORBS1, C21orf63, and KIAA1210 and up-regulation of FABP5, SOX4, and MLP in prostate cancer tissues by TaqMan real-time PCR. Quantitative methylation-specific PCR of PDLIM4, SVIL, PRIMA1, GSTP1, and PTGS2 detected prostate carcinoma with a sensitivity of 94.7%, 75.4%, 47.4%, 89.5%, and 87.7%, and a specificity of 90.5%, 75%, 54.2%, 95.8%, and 90.2%, respectively. Using this panel of methylation markers in combination, we were able to distinguish between prostate cancer and adjacent benign tissues with sensitivities and specificities of about 90% to 100%. Our data provide evidence of transcriptional repression of the putative tumor suppressor gene PDLIM4 by hypermethylation. CONCLUSIONS: Our analysis revealed differential expression of eight down-regulated and three up-regulated genes, implicating their role in prostate cancer development and progression. We further showed that the hypermethylation of PDLIM4 gene could be used as a sensitive molecular tool in detection of prostate tumorigenesis.

PURPOSE:Phyllodes tumor of the prostate is a rare neoplasm of uncertain malignant potential. We studied a large series of phyllodes tumors to define the combination of histological features that are most useful for predicting patient outcome.MATERIALS AND METHODS:A total of 23 cases were obtained from our collective files from 1973 to 2002, and numerous clinical and pathological features were evaluated. A review of the reported cases of phyllodes tumor of the prostate was done.RESULTS:Patient age was 25 to 86 years (mean 55) and they usually presented with urinary obstructive symptoms and hematuria. The diagnosis was made in 18 tumors by transurethral resection, in 2 by enucleation, in 1 by tumor resection and in 2 by prostatectomy. We analyzed 5 histological features, including cellularity (scale of 1 to 3), cytologic atypia (scale of 1 to 3), the number of mitotic figures per 10 high power fields, the stroma-to-epithelium ratio (low or high) and necrosis (present or absent). This combination of features revealed that 14 cases were low grade phyllodes tumor, 7 were intermediate grade and 2 were high grade with the high grade cases characterized by increased cellularity, severe cytological atypia, more than 5 mitotic figures per 10 high power fields and a high stroma-to-epithelium ratio, indicating stromal overgrowth. Immunohistochemical studies of 8 tumors revealed consistent, intense cytoplasmic immunoreactivity in stromal cells for vimentin and actin, in luminal epithelial cells for prostate specific antigen, prostatic acid phosphatase and broad-spectrum keratin AE1/AE3, and in basal cells for high molecular weight keratin 34beta-E12. Recurrence was seen in 7 of 14 low grade tumors (50%) and in 1 patient low grade sarcoma emerged with subsequent distant metastases 14 years after initial diagnosis following 5 recurrences. Recurrence was seen in 6 of 7 intermediate grade tumors and low grade sarcoma emerged with subsequent abdominal wall metastases in 1 patient 11 years after initial diagnosis following 3 recurrences. The phyllodes tumor recurred in each patient with high grade tumors with a time to first recurrence of 6 and 0.2 years, respectively. Distant metastases developed in these 2 patients.CONCLUSIONS:Histological grading of prostatic phyllodes tumors is predictive of short-term outcome based on the combination of stromal cellularity, cytological atypia, number of mitotic figures and the stroma-to-epithelium ratio. However, these tumors usually recur after transurethral prostatic resection and they are often locally aggressive with time. The emergence of overt sarcoma and metastatic disease is more frequent than previously recognized. Complete resection at initial diagnosis appears to be indicated.

We studied the usefulness of a p63/P504S immunostain "cocktail" in evaluation of prostate biopsy specimens containing atypical acini suspicious for adenocarcinoma (AASA), high-grade prostatic intraepithelial neoplasia (HPIN), and small foci of adenocarcinoma and tested the sensitivity and specificity of the immunostain with tissue microarrays (TMAs) constructed from prostatectomy and lymphadenectomy specimens. We selected 40 cases containing a focus of adenocarcinoma (14 cases), AASA (7 cases), AASA with HPIN (7 cases), HPIN (6 cases), and atypical favor benign (6 cases). After p63/P504S immunostaining, 13 cases (33%) were reclassified: AASA with HPIN to HPIN only in 5 cases (13%), atypical favor benign to benign in 4 cases (10%), AASA to adenocarcinoma in 2 cases (5%), and atypical favor benign to AASA and atypical favor benign to HPIN in 1 case (3%) each. The diagnosis of adenocarcinoma was supported by immunostain in 14 cases. In TMA studies, the p63/P504S immunostain for adenocarcinoma and HPIN had sensitivity values of 97.2% and 86.2%, respectively, and specificity values of 99.7% and 81.6%, respectively. P504S stained 64 (74%) of 87 cores of metastatic cancers, and no p63-positive cells were identified in the metastases. The p63/P504S immunohistochemical stain is a sensitive, specific marker for prostatic adenocarcinoma and HPIN and useful in the evaluation of AASA in biopsy specimens.

We assessed diagnostic criteria among 38 spindle cell tumors of the urinary bladder and obtained follow-up in 36 patients. Patients comprised 28 males and 10 females aged 2.5 months to 87 years. Hematuria was the commonest presenting symptom (27 patients). After review and immunohistochemical workup, 17 patients had inflammatory pseudotumor (myofibroblastic tumor), 4 postoperative spindle cell nodule, 1 leiomyoma, 13 sarcoma (7 low-grade; 6 high-grade), and 3 carcinoma. Mean age was 38 years for pseudotumor (range 15 to 74), 65 for postoperative spindle cell nodule, 51 for sarcoma, and 76 for carcinoma. Size of pseudotumor averaged 4.4 ± 0.7 cm (range 1.5 to 13.0), similar to sarcoma, 4.0 ± 0.6 cm (range 0.5 to 7.0). Similar proportions of benign tumors and sarcomas had muscularis propria invasion. The criteria that best differentiated sarcoma from inflammatory pseudotumor were presence of necrosis at the tumor-detrusor muscle interface in muscle-invasive cases, and nuclear atypia. Sarcoma also had less prominent microvasculature, less variable cellularity, consistently ≥1 mitotic figure per 10 high-power fields, and predominant acute inflammation without plasma cells. p53 protein nuclear immunostaining was moderate, unlike the rare to absent staining in pseudotumors. Because all 12 sarcomas were desmin-negative, we did not call them leiomyosarcoma; they overlapped with benign tumor in epithelial, mesenchymal, and actin immunostaining. Among 12 sarcoma patients, 2 died of tumor (at 3 months). Two of four experienced tumor recurrence after partial cystectomy (2 and 26 months). No pseudotumors recurred after transurethral resection or partial cystectomy, although one patient, 5 months after transurethral resection, had histologically identical pseudotumor that the surgeon considered residual. Another patient with pseudotumor, not a candidate for tumor ablation after transurethral resection, had continued tumor growth and he died of urosepsis. In conclusion, inflammatory pseudotumor, although overlapping with sarcoma in presentation, age range, and size, does not metastasize and remains histologically distinct from low-grade sarcoma.

We compared the grading and staging of transurethral resection of the bladder (TURB) and cystectomy specimens for 105 patients who underwent radical cystectomy for urothelial carcinoma between 1980 and 1984. Of 105 patients, 96% underwent cystectomy within 100 days of TURB (median interval, 10 days). Grading was performed according to the 1998 World Health Organization/International Society of Urologic Pathology grading system and staging according to the 1997 TNM classification. Histologic grade was low-grade, 13; high-grade, 92 in TURB specimens; low-grade, 17; high-grade, 88 in cystectomy specimens. Pathologic stage was Ta, 15; T1, 55; and T2, 35 in TURB specimens; Ta, 5; T1, 19; T2, 19; T3, 46; and T4, 16 in cystectomy specimens. Histologic grade at TURB was associated with pathologic stage at cystectomy (P < .001). When all advanced-stage (muscle-invasive) carcinomas (pT2 or more) were considered together, 55 patients were understaged by TURB, 4 had higher stage in TURB than in cystectomy, and 46 were the same stage as by cystectomy. Forty-three of 55 patients with stage T1 carcinoma at TURB had advanced-stage carcinoma at cystectomy, including 34 who had extravesicular extension (pT3 or more). We found pathologic understanding by TURB occurs in a significant number of patients with bladder cancer; the newly proposed grading system predicted final pathologic stage.

BACKGROUND:In the 1998 World Health Organization and International Society of Urologic Pathology (WHO/ISUP) classification system for bladder neoplasms, flat intraepithelial lesions of the urinary bladder were categorized as reactive atypia, atypia of unknown significance, dysplasia, and carcinoma in situ. The clinical outcomes of patients diagnosed with these atypical urothelial proliferations are uncertain. METHODS:The authors studied a series of patients who were diagnosed with reactive atypia of the urinary bladder (25 patients), urothelial atypia of unknown significance (35), or urothelial dysplasia (26) between 1985 and 1993. All histologic slides were reviewed and classified according to the 1998 World Health Organization and International Society of Urologic Pathology classification system. Patients with a concomitant or prior history of carcinoma in situ or urothelial carcinoma were excluded. RESULTS:Patient age at diagnosis ranged from 24 to 88 years (mean, 65 years). The male-to-female ratio was 3:1. The mean follow-up was 3.9 years (range, 0.1-13.4 years; median, 3.5 years). None of the patients with reactive atypia or atypia of unknown significance developed dysplasia, carcinoma in situ, or urothelial carcinoma. Four patients (15%) with urothelial dysplasia developed biopsy-proven cancer, including 3 patients with muscle-invasive cancer. The mean interval from the diagnosis of urothelial dysplasia to the development of cancer was 4.5 years. CONCLUSIONS:Patients with a diagnosis of urothelial atypia of unknown significance or reactive atypia do not have adverse clinical outcomes, whereas patients with urothelial dysplasia of the bladder have an increased risk for the development of carcinoma in situ and urothelial carcinoma.

BACKGROUND. Paraganglioma of the urinary bladder is rarely encountered and its biologic behavior is uncertain. The authors sought to determine the prognostic factors that would predict patient outcome.METHODS. The Mayo Clinic experience over 53 years with paraganglioma of the bladder was reviewed. All histologic slides from 16 patients were reviewed by the authors. Eight cases were examined immunohistochemically with cytokeratin (AE1/3, cytokeratin 7, and cytokeratin 20), vimentin, S-100 protein, neuroendocrine markers (chromogranin, synaptophysin, and neuron specific enolase), p53 protein, and MIB-1. DNA ploidy was determined by digital image analysis in formalin fixed, paraffin embedded tissue. The mean follow-up was 6.3 years (range, 0.4-16.4 years).RESULTS. Paraganglioma usually occurred in young adult women (mean age, 45 years; range, 16-74 years). The male-re-female ratio was 1 to 3. The common symptoms and signs were hypertension and hematuria. The rumors were usually located intramurally in the lateral and posterior wall of the bladder and were multifocal in 3 cases (18%). Seven patients were treated by transurethral resection, eight by partial cystectomy, and one by radical cystectomy. T classification was T1 (1 patient), T2 (9 patients), T3 (2 patients), and T4b (4 patients). Ar the time of diagnosis, one patient had distant metastasis and one had regional lymph node metastasis. One patient developed metastasis 1 year after diagnosis and died of the disease 1.5 years later. None of the patients with T1 or T2 tumors had recurrence or tumor progression. All tumors were aneuploid. The mean MIB-1 labeling index was 1.5% (range, 0.03-7.0%). The tumor cells displayed immunoreactivity for S-100 protein and neuroendocrine markers and were negative for p53 (except 1 case) and cytokeratin.CONCLUSIONS. Paraganglioma of the urinary bladder occurs mostly in young adult women. Patients with tumor of advanced classification (greater than or equal to T3) are at risk of recurrence, metastasis, and dying of the disease, whereas patients in this study with T1 or T2 disease had favorable outcomes after complete tumor resection. (C) 2000 American Cancer Society.

BACKGROUND. Clinical outcomes vary for patients treated with radical cystectomy. The authors sought to identify factors associated with the survival of patients treated with radical cystectomy for urothelial carcinoma of the urinary bladder.METHODS. The authors studied 218 patients treated with radical cystectomy for urothelial carcinoma between 1980 to 1984. Patient ages ranged from 41 to 78 years (mean, 64 years). Using the 1997 TNM system, T classifications were Ta (17 patients), T1 (44), T2 (71), T3a (42), T3b (14), T4a (28), and T4b (2). Thirty-two patients had lymph node metastasis at the time of surgery. Histologic grade was determined according to the newly proposed World Health Organization and International Society of Urological Pathology grading system; tumor was low grade in 43 patients and high grade in 175. The male-to-female ratio was 4.9 to 1. The mean follow-up of patients still alive was 13.1 years (median, 13.8 years; range, 30 days to 18 years). Cox proportional hazards models were used to determine the impact of numerous clinical and pathologic findings on survival.RESULTS. Ten-year local recurrence free, distant metastasis free, cancer specific, and all-cause survival were 71%, 73%, 67%, and 41%, respectively. In univariate analysis, cancer size, T classification, and lymph node status were associated with distant metastasis free, cancer specific, and all-cause survival. Histologic grade and surgical margin status were significantly associated with worse cancer specific and all-cause survival, but not with distant metastasis free survival. In multivariate analysis, cancer size, margin status, T classification, and lymph node status were identified as significantly associated with cancer specific survival after adjustment for age and gender.CONCLUSIONS. Long term survival is achieved in a significant number of patients treated with radical cystectomy. In this study, patients with organ-confined (less than or equal to pT2) and small size (less than or equal to 3 cm) cancer had favorable 10-year distant metastasis free (93%) and cancer specific survival (88%) after cystectomy. Tumor size, margin status, extravesical involvement, and lymph node metastasis are important pathologic factors and should be considered as stratification variables in identifying patients for whom adjuvant chemotherapy should be evaluated in clinical trials. Cancer 2000;88:2326-32. (C) 2000 American Cancer Society.

BACKGROUND. Urothelial carcinoma of the bladder often contains areas with different histologic grades. The Influence of cancer heterogeneity on grading and its relation to patient outcome is uncertain.METHODS. The study group consisted of 164 patients with Ta urothelial carcinoma diagnosed at the Mayo Clinic between 1985 and 1986. None had previous or coexistent urothelial carcinoma in situ or invasive carcinoma. The primary (most common) and secondary (second most common if at least 5% of the cancer) patterns of cancer growth were graded by the newly proposed World Health Organization and International Society of Urological Pathology (WHO/ISUP) grading system. Scores of 1, 2, and 3 were assigned to urothelial neoplasms of low malignant potential (LMP), low grade urothelial carcinoma, and high grade urothelial carcinoma, respectively. The mean follow-up was 7.7 years (range, 0-13.3 years; median, 9.2 years). Progression was defined as the development of invasive carcinoma, distant metastasis, or death due to bladder carcinoma.RESULTS. Patient ages ranged from 36 to 96 years (mean, 69 years), and the male-to-female ratio was 4:1. Disease progression developed in 32 patients during a mean follow-up of 7.7 years. The mean interval from diagnosis to progression was 3.1 years (range, 0.01-8.7 years). Progression free survival was 82%, 77%, and 76% at 5, 7, and 10 years, respectively. Primary and secondary grades were different for 52 patients (32%). Based on the worst grade, 19 patients (12%) had urothelial neoplasms of low malignant potential (LMP), 92 (56%) had low grade carcinoma, and 53 (32%) had high grade carcinoma. Histologic grades based on worst, primary, secondary, and combined primary and secondary grades were all significant for predicting progression (P = 0.0009, 0.0004, 0.001, and 0.0001, respectively). Seven-year progression free survival rates for patients with LMP, low grade, and high grade carcinoma (based on worst grade) were 93%, 82%, and 61%, respectively; for patients with combined scores of 2, 3, 4, 5, and 6, survival rates were 93%, 80%, 82%, 68%, and 40%, respectively. The difference between patients with combined scores of 5 or 6 was statistically significant (P = 0.02).CONCLUSIONS. Histologic grade of urothelial carcinoma based on the newly proposed WHO/ISUP grading system stratifies patients into prognostically significant groups. Grading should also take cancer heterogeneity into consideration, and prognostic accuracy appears to be increased when the combined primary and secondary grades are applied. [See editorial counterpoint on pages 1509-12 and reply to counterpoint on pages 1513-6, this issue.] (C) 2000 American Cancer Society.

BACKGROUND. Accurate examination of radical cystectomy specimens is critical for stratifying patients into prognostically important groups and determining the need for adjuvant treatment. Evidence has accumulated that cancers invading the superficial muscle wall (T2a) behave similarly to those invading the deep muscle wall (T2b). Quantitative analysis of the depth of invasion in relation to patient outcome is needed.METHODS, The authors systematically evaluated the depth of invasion by micrometer measurement and its relation to the survival of 64 patients with bladder carcinoma pathologic classification as pT2 who had long term follow-up after radical cystectomy. Numerous clinical and pathologic variables were analyzed with univariate and multivariate Cox proportional hazards models. The mean age of patients was 64 years, and their mean follow-up was 8.3 years.RESULTS. There was no significant difference in clinical outcome between patients with T2a carcinoma and those with T2b. Lymph node metastasis and tumor size were each significantly associated with distant metastasis free and cancer specific survival. Ten-year distant metastasis free and cancer specific survival were 100% and 94%, respectively, for patients with tumors <3 cm (P = 0.006) and 68% and 73%, respectively, for patients with tumors greater than or equal to 3 cm (P = 0.005). After adjustment for lymph node status, tumor size maintained significance in predicting distant metastasis free survival (risk ratio, 1.5; 95% confidence interval, 1.1-2.0; P = 0.009) and cancer specific survival (risk ratio, 1.5; 95% confidence interval, 1.1-1.9; P = 0.01). Age was associated with recurrence free survival and all-cause survival. None of the other variables, including gender, vascular invasion, presence of carcinoma in situ, pathologic classification (T2a vs. T2b), depth of invasion, depth of muscle invasion, ratio of depth of invasion to bladder wall thickness, and percentage of muscle wall invasion, were significantly associated with patient outcome.CONCLUSIONS, The findings of this study indicate that the subclassification of T2 bladder carcinoma by depth of muscle invasion is of no prognostic value; conversely, tumor size, an easily measured factor, is predictive of distant metastasis free and cancer specific survival. Cancer 1999;85:2638-47, (C) 1999 American Cancer Society.

BACKGROUND:A significant number of T1 bladder carcinoma patients are understaged by transurethral resection of the bladder (TURB), indicating a substantial need for more accurate staging. METHODS:The authors studied 55 patients with T1 bladder carcinoma detected by TURB at the Mayo Clinic between December 1979 and July 1984. The mean age of the patients was 66 years (range, 50-78 years). All patients were treated by cystectomy. The median interval from TURB to cystectomy was 10 days. Grading was performed according to the 1998 World Health Organization/International Society of Urologic Pathology grading system. The 1997 TNM classification was used for pathologic staging. In addition, the depth of invasion was measured from the mucosal basement membrane by micrometer. Receiver operating characteristic (ROC) analysis was used to evaluate the usefulness of depth of invasion as a marker for advanced stage bladder carcinoma (>/= T2). RESULTS:The final pathologic stages were Ta (2 patients), T1 (10 patients), T2a (9 patients), T2b (13 patients), T3 (11 patients), and T4 (10 patients) at cystectomy. There was a significant correlation between the depth of invasion at TURB and the final pathologic stage (Spearman correlation coefficient = 0.63; P < 0.001). The overall accuracy for the prediction of advanced stage (>/= T2) bladder carcinoma as measured by the area under the ROC curve was 0.89 (standard error, 0.05). Using 1.5 mm as a threshold (with >1.5 mm indicating advanced stage disease), the sensitivity, specificity, and positive and negative predictive values were 81%, 83%, 95%, and 56%, respectively. Histologic grade at the time of TURB also was associated significantly with final pathologic stage at cystectomy (P = 0.03) whereas stratification of patients according to invasion above or below the muscularis mucosae at TURB was not a significant predictor of final pathologic stage. CONCLUSIONS:The results of the current study show that substaging of T1 bladder carcinoma according to the depth of invasion (as measured by micrometer) provides significant prognostic information. Therefore the authors recommend that it be reported in specimens obtained by TURB.

High-grade prostatic intraepithelial neoplasia (PIN) is the most likely precursor of prostate cancer. The effect of radiation therapy (RT) on the prevalence of PIN is uncertain. We studied 86 patients who underwent salvage radical prostatectomy after irradiation failure at the Mayo Clinic. The prevalence, volume, multicentricity, spatial proximity to cancer, and architectural patterns of PIN were evaluated. High-grade PIN was identified in 53 (62%) of 86 prostatectomy specimens. Multiple architectural patterns were usually observed, including tufting in 87%, micropapillary in 66%, cribriform in 38%, and flat in 17%. The mean volume of PIN was 0.12 cm3 (range, 0.05-1.20 cm3). PIN was usually multicentric (70%), with a mean number of PIN foci of 2.5 (range, 1-10). Ninety-four percent of PIN foci were located within 2 mm of invasive cancer. There was no correlation between PIN and pathologic stage, surgical margin, tumor size, DNA ploidy, post-RT Gleason score, time interval from RT to biopsy-proven recurrence, postoperative prostate-specific antigen level, distant metastasis-free survival, or cancer-specific survival. Our examination of salvage radical prostatectomy specimens indicated that the prevalence and extent of PIN appeared to be reduced after RT compared to published studies of prostatectomies without prior RT.

PURPOSE:A significant number of patients with stage T1 bladder carcinoma are at risk for cancer progression. We sought to identify factors associated with cancer progression in a series of patients with stage T1 bladder carcinoma treated with a contemporary therapeutic approach. PATIENTS AND METHODS:The study population consisted of 83 consecutive patients in whom stage T1 bladder carcinoma was diagnosed at the Mayo Clinic between 1987 and 1992. All patients underwent transurethral resection of the bladder (TURB) and had histologic confirmation of the diagnosis. The mean age was 71 years (range, 47 to 94 years). The male-to-female ratio was 3.9:1. The mean length of follow-up was 5.2 years (range, 1 day to 10.4 years). The depth of lamina propria invasion in the TURB specimens was measured with an ocular micrometer. Cancer progression was defined as the development of muscle-invasive or more advanced stage carcinoma, distant metastasis, or death from bladder cancer. RESULTS:The overall 5- and 7-year progression-free survival rates were 82% and 80%, respectively. The depth of invasion in the TURB specimens was associated with cancer progression (hazards ratio, 1.6 for doubling of depth of invasion; 95% confidence interval, 1.03 to 2.4; P =.037). The 5-year progression-free survival rate for patients with depth of invasion of >/= 1.5 mm was 67%, compared with 93% for those with depth of invasion of less than 1.5 mm (P =.009). No other variable, including age, sex, tobacco use, alcohol use, the presence of carcinoma-in-situ, histologic grade, lymphocytic infiltration, or muscularis mucosae invasion, was associated with cancer progression. CONCLUSION:The depth of invasion in the TURB specimens, measured with a micrometer, is predictive of cancer progression in patients with stage T1 bladder carcinoma.

BACKGROUND. An international consensus has been reached regarding diagnostic criteria for papilloma of the urinary bladder. However, the incidences of recurrence and progression in patients with urothelial papilloma are uncertain.METHODS. The population for this study consisted of 52 patients who were diagnosed with urothelial papilloma of the bladder at the Mayo Clinic between 1914 and 1998. All histologic slides were reviewed and fulfilled the diagnostic criteria of urothelial papilloma from the 1998 World Health Organization/International Society of Urological Pathology classification system. No patients had previous or coexistent urothelial carcinoma, and none were treated after biopsy.RESULTS. The mean patient age at diagnosis was 57 years (range, 22-89 years). The male-to-female ratio was 1.9:1. The mean Follow-up was 9.8 years (range, 0.1-58 years). Four patients developed recurrent papilloma (mean interval from diagnosis to recurrence, 3.3 years); 1 other patient developed papillary neoplasm of low malignant potential (Ta WHO Grade 1 papillary urothelial carcinoma) 6 years after the initial diagnosis of papilloma. None of these patients developed dysplasia, carcinoma in situ, or invasive urothelial carcinoma or died of bladder cancer.CONCLUSIONS. Patients with urothelial papilloma have a low incidence of recurrence and rarely, if ever, develop urothelial carcinoma; [See editorial on pages 1890-2 and related article on pages 2102-8, this issue.] Cancer 1999;86:2098-101. (C) 1999 American Cancer Society.