Improved detection of urothelial carcinomas with fluorescence immunocytochemistry (uCyt+ assay) and urinary cytology: results of a French Prospective Multicenter Study

The aim of the study was to assess the sensitivity and specificity of fluorescence immunocytochemistry (uCyt+ assay) as combined with urinary cytology for detection of primary and recurrent urothelial carcinomas. We analyzed 694 urinary samples from 236 new symptomatic patients and 458 patients followed after transurethral resection (TUR) for bladder tumor. Lesions suspicious for cancer at cystoscopy were sampled by biopsies or TUR. Sensitivity and specificity of tests were calculated using cystoscopy and histopathology, whether or not combined as gold standards. In new symptomatic patients, sensitivity of uCyt+ was 40%, 88.2%, and 76.7%, whereas that of urinary cytology was 30%, 70.6%, and 83.3%, respectively, in G1, G2, and G3 tumors. In follow-up cases, sensitivity of uCyt+ was 61.9%, 66.7%, and 76.9%, whereas that of urinary cytology was 38.1%, 58.3%, and 64.1%, respectively, in G1, G2, and G3 tumors. The combination of uCyt+ and urinary cytology significantly increased mean sensitivity in newly diagnosed cases (86.4% versus 71.2% with urinary cytology only, p < 0.05), as well as in patients followed after TUR (79.3% versus 55.2%, p < 0.001). Specificity of uCyt+ and urinary cytology was identical in new patients (83.3%) and was 81.9% and 86.2%, respectively, in patients followed after TUR. In patients with negative cystoscopy, positive uCyt+ tests had a strong predictive value for tumor recurrence at 1 year (47.0% versus 11.9% in patients with negative assay, p < 0.01). We conclude that combining uCyt+ with urinary cytology improves the detection of urothelial carcinomas as well in patients with symptoms suggesting bladder cancer as in those followed after treatment.     

Evaluation of fluorescence in situ hybridization as an ancillary tool to urine cytology in diagnosing urothelial carcinoma

Our purpose was to evaluate the feasibility of performing fluorescence in situ hybridization (FISH) on routine urine samples and to compare the relative sensitivities of urine cytology and FISH for detecting urothelial carcinoma. Light microscopy (LM) using cytologic evaluation and FISH were used to study 121 consecutive urine samples. A mixture of fluorescent probes to chromosomes 3, 7, 17, and the 9p21 locus were used for detection of numerical chromosomal abnormalities (UroVysion, Vysis/Abbott). Biopsy specimens from patients in the study were reviewed if available. FISH analysis was performed without knowledge of cytology or biopsy findings. The urine cytology of 121 samples was interpreted as 59 negative, 41 reactive, 16 atypical, 2 suspicious and 3 insufficient cells for diagnosis. 85 samples were successfully analyzed by FISH. Thirty-one of these showed chromosomal abnormalities and these samples were initially regarded on the original cytology reading as follows: 10 negative, 10 reactive, 9 atypical, and 2 suspicious. FISH demonstrated chromosomal abnormalities in a significant number of cases (67%) that were initially diagnosed as normal or reactive by LM. Twenty-five patients were identified who had biopsy-proven TCC and successful FISH. Thirteen of the 25 patients (52%) were abnormal by FISH (cytology: 2 suspicious, 6 atypical, 4 reactive, 1 negative). One patient was atypical by cytology with normal FISH results but had TCC on biopsy. Hyperdiploidy for chromosomes 3 (77%) and 7 (67%) were seen consistently. Multiple chromosomal abnormalities were seen in 67% of these cases. We conclude that FISH has a greater sensitivity in detecting urothelial carcinoma when coupled with urine cytology. It is not entirely clear at this time whether a positive FISH may indicate frank neoplastic urothelial transformation or merely be an indicator of unstable urothelium capable of or primed for malignant transformation thus detecting patients at significant risk. The use of FISH in conjunction with urine cytology can potentially reduce urothelial carcinoma morbidity and mortality by diagnosing these tumors earlier.     

Utility of a multiprobe fluorescence in situ hybridization assay in the detection of superficial urothelial bladder cancer

We evaluated the performance of a multiprobe FISH (fluorescence in situ hybridization) assay for noninvasive detection of superficial urothelial carcinoma (UC) in the bladder, in comparison to urinary cytology. Voided urine samples from 74 patients with superficial UC were analyzed by both techniques. Urine samples from 19 patients with muscle-invasive tumors and from 19 healthy control subjects were also studied. For FISH analysis, labeled probes for chromosomes 3, 7, 9, and 17 were used to assess chromosomal abnormalities indicative of malignancy. We found a significant difference between the overall sensitivity of FISH and cytology in superficial UC detection (70.3 versus 35.1%, respectively; P < 0.0001). This significant difference was maintained when superficial UCs were broken down into low grade (52.8 versus 13.9%, respectively; P < 0.0005) and high grade (86.8 versus 55.3%, respectively; P < 0.0015) tumors. Overall specificity was 100% for cytology and 94.7% for FISH (difference not significant). Of patients with suspicious cytology, 69% were positive by FISH. Together, these findings suggest that FISH assay for chromosomes 3, 7, 9, and 17 has a higher sensitivity than cytology and a similar specificity in the detection of superficial UC--which could be useful for reducing some cystoscopies in the accurate follow-up usually performed in these patients.     

Multiprobe FISH for enhanced detection of bladder cancer in voided urine specimens and bladder washings.

The aim of this study was to evaluate the UroVysion (Vysis, Downers Grove, IL) fluorescence in situ hybridization (FISH) test for improved detection of bladder cancer in urinary specimens. Three groups of specimens were examined, including voided urine specimens (1) collected before resection of bladder cancer, (2) from cystoscopically negative bladders of patients with previous bladder cancer, and (3) from patients with benign prostatic hyperplasia (controls). FISH positivity was defined as more than 2 urothelial cells with an abnormal signal copy number of at least 1 of the 4 probes. FISH was positive in 1 of 27 control specimens and in 33 (73%) of 45 pTa, 12 (100%) of 12 pT1, and 13 (100%) of 13 pT2-4 tumors. The results were similar in a series of 68 bladder washings. In addition, FISH of voided urine specimens was positive in 5 of 10 patients with negative follow-up cystoscopy results. Subsequent recurrence was found in 4 of these patients but in none of 5 patients with FISH-negative results. Multiprobe FISH markedly improves the sensitivity and specificity of cytology for the detection of bladder cancer in urine specimens.     

Routine transurethral biopsy of the bladder is not necessary to evaluate the response to bacillus calmette-guerin therapy

We evaluated the need for transurethral biopsy at first follow-up after intravesical bacillus Calmette-Guerin (BCG) therapy for superficial bladder cancer. The records of 84 patients with superficial bladder cancer who received a 6- or 8-week course of BCG were reviewed. Pathological results before BCG, cystoscopic findings, urinary cytology, and biopsy results for evaluation of BCG therapy were reviewed. All 19 patients with positive urinary cytology had evidence of positive bladder biopsy results. Fifty-three of 54 patients (98.1%) with no visible recurrent tumor and negative urinary cytology demonstrated negative pathological results on bladder biopsy. When not found in conjunction with positive urinary cytology, erythematous mucosa on cystoscopy was not an indicator of tumor recurrence or residual cancer. In conclusion, routine transurethral biopsy of the bladder for evaluating the response to BCG intravesical therapy is not necessary in patients who have no visible tumor on cystoscopy and negative urinary cytology.     

ImmunoCyt/uCyt+ improves the sensitivity of urine cytology in patients followed for urothelial carcinoma.

ImmunoCyt/uCyt is a fluorescent test combining three monoclonal antibodies. In this study, it has been tested as a complement to cytology in the detection of urothelial carcinoma in urine. It has been performed simultaneously with standard cytology and cystoscopy on 870 urine analyses from one hospital. In 136 cases, one or more bladder tumors were found. Overall sensitivity of cytology, ImmunoCyt/uCyt and combined analyses reached 29, 74 and 84%, respectively, and overall specificity was 98, 62 and 61%. The negative predictive value of cytology, ImmunoCyt/uCyt and both analyses was 88, 93 and 95%, respectively, and the positive predictive value was 70, 26 and 29%. The sensitivity of cytology for low malignant potential neoplasms, low- and high-grade papillary carcinomas was 6, 18 and 53%, while it reached 71, 79 and 93% when combined with ImmunoCyt/uCyt. The sensitivity of cytology for stages Ta, T1, T2 and over and Tis tumors was 12, 67, 47 and 50%, while it reached 78, 83, 79 and 100% when combined with ImmunoCyt/uCyt. In the absence of tumor on cystoscopy but with positive ImmunoCyt/uCyt, 18% of patients developed a tumor, 2-6 months later. Of the 109 cases diagnosed as suspicious for malignancy by cytology, a tumor was present in 30 cases and ImmunoCyt/uCyt was positive in 22 (73%) of them. In conclusion, ImmunoCyt/uCyt may be used to postpone cystoscopies in patients followed for bladder cancer and may help to save cytologist and pathologist screening time.     

Clinical significance of signal pattern of high-risk human papillomavirus using a novel fluorescence in situ hybridization assay in cervical cytology

The present study aimed to evaluate a novel fluorescence in situ hybridization (FISH) assay for detecting the high-risk human papillomavirus (HR-HPV) DNA and signal pattern in cervical cytology specimens and for identifying cervical intraepithelial neoplasia (CIN) lesions. One hundred and ninety-six liquid-based cytology specimens with CIN were recruited. The signal pattern (punctate, mixed punctate and diffuse, and diffuse) detected by FISH was compared with E6 mRNA and correlated with histological classification. FISH and E6-type specific polymerase chain reaction (PCR) had fair to good agreement for detecting HPV DNA across all grades of CIN (kappa coefficient, 0.37–0.73). Among 44 samples of negative FISH and positive E6 type-specific PCR in HPV 16, 18, 31, 33, 52 and 58, 82% (36/44) of E6 mRNA were not detected, in contrast to 41% (48/118) of positive FISH and positive E6 type-specific PCR (p <0.0001). Among HR-HPV DNA positive cases tested by the FISH assay, the specificity of predicting CIN3 using the punctuate pattern is higher than that using E6 mRNA (96.3% vs. 44.8%). The punctate pattern was 0% in patients with <CIN1 lesions, 8.7% for CIN1 lesions, 6.1% for CIN2 lesions, and 34.0% for CIN3 lesions (p 0.001). The odds ratios were 8.7-fold higher (2.7–27.8, p <0.0001) for the punctate pattern versus the mixed punctate and diffuse pattern, and the diffuse pattern, for predicting CIN3 lesions. The novel FISH assay is comparable to PCR for detecting HPV DNA in cervical cytology with CIN lesions. The punctate signal pattern detected by the FISH assay can be more biologically and clinically relevant for clinically detecting CIN3 lesions.     

Cytology,flow cytometry,image analysis,and interphase cytogenetics by fluorescence in situ hybridization in the diagnosis of transitional cell carcinoma in bladder washes: A comparative study

The diagnosis of transitional cell carcinoma (TCC) in bladder washes is a diagnostic challenge to cytology. This study assessed the role of flow cytometry (FCM), image analysis (IA), and interphase cytogenetics by fluorescence in situ hybridization (FISH) as adjuncts in the cytodiagnosis of TCC in bladder washes. Forty separate samples of bladder washes were prospectively evaluated by conventional cytology (CY), FCM, IA, and FISH, and the results were compared with the subsequent surgical biopsy specimens which revealed 26 TCC (3 GR I, 6 GR II, 17 GR III) and 14 benign lesions. Using histology as the “gold standard” and following the previously published criteria for detection of TCC by CY, FCM, IA, and FISH, the concordance rates between histology and CY, FCM, IA, and FISH were 75, 74, 89, and 83%, respectively. CY, FCM, IA, FISH, and histology were concordant in 54% of the cases. The sensitivity of CY, FCM, IA, and FISH were 61, 72, 91, and 73%. respectively, while the specificity were 100, 80, 83, and 100%, respectively. The combined sensitivity of all the parameters was 96%. Interestingly, the false positive cases by FCM and IA showed cystitis. We conclude that IA has the highest sensitivity in detecting TCC in bladder washes followed by FISH, FCM, and CY, while CY and FISH have the highest specificity. This study indicates that FCM, IA, and FISH are useful adjuncts to cytology in the diagnosis of TCC in bladder washes. The finding of DNA-aneuploidy in cystitis warrants further investigation. © 1995 Wiley-Liss, Inc.     

人端粒酶RNA基因荧光原位杂交检测在宫颈细胞学检查中的应用

目的 探讨人类染色体端粒酶RNA基因(hTERC)扩增的荧光原位杂交(FISH)检测在宫颈脱落细胞防癌筛查中的意义.方法 收集2008年2-10月上海长海医院门诊就诊146例患者宫颈液基细胞学样本,应用间期双色FISH技术检测hTERC基因的扩增情况,并与细胞学和组织学结果进行对照.结果 杂交成功120例(细胞学阴性20例、细胞学阳性100例).hTERC基因扩增的阳性率与细胞学等级成正相关(r=0.465,P＜0.01),与组织学等级成正相关(r=0.610,P＜0.01),各级的阳性率分别为:炎性病变0(0/13)、宫颈上皮内瘤样病变(CIN)Ⅰ级2 8.6%(6/21)、CINⅡ级11/18、CINⅢ级75.0%(18/24)、鳞状细胞癌91.7%(22/24);FISH方法检出高级别(CINⅡ/Ⅲ级)以上病变的敏感性为77.3%(51/66),特异性为82.4%(28/34).阳性预测值89.5%,阴性预测值65.1%,低级别(CIN Ⅰ级)以下病变的hTERC阳性率与高级别以上病变相比差异有统计学意义(x2=32.550,P＜0.01).结合hTERC高倍扩增(信号数＞4)的出现,检出高级别以上病变的敏感性提高到81.2%.结论 hTERC基因扩增的FISH检测有助于辅助细胞学诊断,提高高危病变的检出率.实验结果判断除参照阈值之外,还应结合hTERC基因的扩增类型,出现高倍扩增亦提示高级别以上病变.

Abstract：

Objective To investigate the value of fluorescence in situ hybridization (FISH)detection of human telomerase RNA component ( hTERC ) gene amplification in screening of cervical lesions.Methods A total of 146 post-thinPrep cytology test (TCT) samples were analyzed using FISH by two-color interphase probe targeting hTERC gene at chromosome 3q26 and the data were compared with the cytological and histological results. Results FISH analysis was successful in 120 cases (20 cases of normal and 100 abnormal cases by TCT). Gene amplification of hTERC by FISH had a positive correlation with the cytological (r = 0. 465, P ＜ 0. 01 ) and histological grade results ( r = 0. 610, P ＜ 0. 01 ). Extra copies of hTERC were seen in 28.6% (6/21) of CIN Ⅰ , 61.1% (11/18) of CIN Ⅱ , 75.0% (18/24) of CIN Ⅲ and 91.7% (22/24) of squamous cell carcinoma, respectively. None (0/13) of the inflammation cases showed hTERC amplification. The sensitivity and specificity for detecting high grade lesions by FISH were 77. 3%(51/66) and 82. 4% (28/34) ;and the positive and negative predictive values were 89. 5% and 65. 1%,respectively. The rate of hTERC gene gain in high grade lesions was significantly higher than that in the low grade lesions( x2 =32. 550,P ＜0. 01 ). Combined with the high copy numbers, the sensitivity for detecting high grade lesions was increased to 81.2%. Conclusions Detection of hTERC gene amplification by FISH improves the screening efficiency of high-risk cervical epithelial lesions. The presence of high copy numbers of hTERC correlates with the presence of high grade cervical dysplasia.     

The value of cystoscopy as an initial diagnostic modality for asymptomatic microscopic hematuria.

For the patients who visit outpatient clinics due to asymptomatic microscopic hematuria, cystoscopy has been looked upon as rather invasive compared to other diagnostic methods. We tried to elucidate the actual diagnostic value of cystoscopy in the initial evaluation of asymptomatic microscopic hematuria. We reviewed the results of cystoscopic examinations in 213 patients who visited our hospital due to asymptomatic microscopic hematuria. No definite lesion that could explain the microscopic hematuria was detected by means of IVP, urine cytology, and other nephrologic evaluations for all the patients. Among the abnormal cystoscopic findings in 55 patients, the lesions suspected to be directly related to microscopic hematuria were classified as 'significant lesions' (31 patients, 17.6%) which include entities such as bladder cancer (1.31%). 27 of 31 patients with significant lesions (85.2%) were over 50 yr old, and furthermore, 3 patients who were diagnosed as bladder tumor by cystoscopy were over 60 yr. Cystoscopy should be utilized as initial diagnostic modality in older patients with asymptomatic microscopic hematuria to rule out any possibility of bladder cancer occurrence. Further studies are needed to justify implementation of cystoscopy as an initial diagnostic modality in younger patients with asymptomatic microscopic hematuria.     

Assessment of chromosomal gains as compared to DNA content changes is more useful to detect dysplasia in Barrett's esophagus brush cytology specimens

Abnormal DNA ploidy status has been suggested as a prognostic factor for Barrett's esophagus progression into esophageal adenocarcinoma (EAC). The aim of the study was to compare image cytometry DNA analysis (ICDA) and fluorescent in situ hybridization (FISH) in the assessment of DNA ploidy status in Barrett's esophagus (BE), and to determine the value of these abnormalities as an adjunct to conventional cytology in detection of dysplasia and EAC. Brush cytology specimens of 90 BE patients were examined using ICDA and FISH with peri-centromeric probes for chromosomes 7 and 17. The results of ICDA and FISH were compared with each other, and with dysplasia grade or EAC as determined by histology and cytology. FISH and ICDA detected abnormalities in 41% (37/90) and 22% (19/90) of the BE cases, respectively. Gains of chromosome 7 and/or 17 were present in 13% of nondysplasia cases, which further increased with dysplasia stage, while overall DNA content aneuploidy was detected predominantly in high grade dysplasia (HGD) and EAC. Using FISH results combined with cytology, we were able to identify IND/LGD (indefinite/ low grade dysplasia) with a sensitivity and specificity of 75 and 76%, respectively. FISH alone detected HGD/EAC with a high sensitivity and specificity of 85 and 84%, which was superior to that of cytology alone. Thus, FISH is more sensitive than ICDA to detect chromosomal abnormalities in BE brush cytology specimens. FISH detects chromosomal gains in early stages of BE and represents a valuable adjunct to conventional cytology to detect dysplasia or EAC.     

Expression and function analysis of indoleamine 2 and 3-dioxygenase in bladder urothelial carcinoma

Indoleamine 2, 3-dioxygenase (IDO) is a rate-limiting enzyme for tryptophan metabolism inducing immune tolerance of tumors. The purpose of this study is to investigate IDO expression and its prognostic significance in bladder urothelial carcinoma (BUC). In this study, immunohistochemical staining for IDO expression in BUC tissues (n = 84) and normal bladder tissues (n = 22) was performed. The mRNA expression levels of IDO in BUC and normal bladder were analyzed by quantitative RT-PCR. Survival analysis was performed for the correlation of IDO expression and clinicopathological factors with disease-free survival. Positive expression of IDO was found in 48 of 84 cases in BUC tissues and was significantly correlated with histological classification, histological grade and TNM stage. While IDO expression in normal bladder tissues was expressed in only 4 of 22 (18.2%) cases. Moreover, IDO mRNA levels of BUC were significantly higher than that of normal bladder. We also found that IDO, histological grade and TNM stage were closely associated with DFS. These results indicated that IDO was related to the progression of BUC and might be one of the crucial prognostic factors for BUC.     

Evaluation of upper urinary tract tumors by FISH in Chinese patients

Upper urinary tract tumor (UUTT) usually presents a high grade and stage, and recurs frequently. The aim of this study was to evaluate the utility of a fluorescence in situ hybridization (FISH) assay on chromosomes 3, 7, 9, and 17 as a reliable and noninvasive method for the diagnosis of Chinese patients with UUTT. Urine specimens from 50 patients with UUTT and 25 donors without evidence of urothelial tumors were analyzed by cytology and FISH. Voided urine samples from 20 normal individuals were used to establish the cut-off values for FISH assay. The McNemar test was applied for sensitivity and specificity. The overall sensitivity of FISH was statistically significantly greater than that of cytology (84.0 vs. 40.0%, P=0.000). The overall specificities of FISH and urine cytology were all 96.0% (P=1.000). Polysomy in chromosomes 3, 7, and 17 were 38, 42, and 30%, respectively. Heterozygous and homozygous loss of the p16 locus was found in 36 and 32%, respectively. FISH analysis performed on cells collected from voided urine is feasible, and FISH could prove to be a reliable and less invasive ancillary test and improve the sensitivity of urine cytology in the diagnosis of UUTT.     

Comparison of fluorescence in situ hybridization,NMP22 bladderchek,and urinary liquid‐based cytology in the detection of bladder urothelial carcinoma

The aim of this study is to evaluate the diagnostic values of the fluorescence in situ hybridization (FISH), NMP22 BladderChek, and liquid‐based cytology (LBC) in the detection of bladder urothelial carcinoma (UC). Consecutive voided urine samples were collected from 138 in‐house patients with a variety of urologic conditions and 37 healthy individuals as negative controls. FISH, NMP22 BladderChek, and LBC were performed on the specimens. All three tests were evaluated independently in a blinded fashion. In all, 104 out of the 175 patients enrolled in this study had histologically proven UC. LBC, FISH, and NMP22 BladderChek were successfully performed on 175, 149, and 119 cases, respectively. The three tests revealed overall sensitivities of 73.1%, 86.5%, and 67.6%, respectively. FISH was more sensitive than LBC (P=0.022) and NMP22 BladderChek (P=0.004). Combination of all the tests yielded a superior sensitivity of 96.7% compared with LBC (P<0.001), NMP22 BladderChek (P<0.001), and FISH (P=0.016), with the specificity only decreased slightly. Sensitivities of the three tests enhanced significantly with increasing UC grade (P<0.05). The positive rates of FISH and NMP22 BladderChek in equivocal cytologic diagnoses were 85.7% and 61.9% in UC, and 37.5% and 50.0% in non‐UC (FISH: P=0.021; NMP22 BladderChek: P=0.683). FISH was more sensitive than LBC and NMP22 BladderChek. FISH had the ability to clarify equivocal cytologic diagnoses. Combination of all three tests showed an improvement in the sensitivity compared to any single test alone in detecting UC with the specificity slightly decreased. Diagn. Cytopathol. 2013;41:852–857. © 2013 Wiley Periodicals, Inc.     

Utility of the BTA stat test kit for bladder cancer screening.

Our study evaluated the BTA (bladder tumor antigen) stat test kit as a primary screening device for the detection of transitional-cell carcinoma (TCC) of the bladder, with direct comparison by voided urine cytology (VUC) on the same specimens. The unfixed voided urine of 100 patients with no history of bladder cancer who had signs and symptoms of dysuria, incontinence, and gross hematuria and microhematuria were tested using the one-step BTA stat test kit before processing via the cytospin technique for fluid cytological evaluation. The patients in the study were followed for up to 12 mo with repeated urine cytological testing, cystoscopy, and bladder biopsy when clinically indicated. Nineteen cases tested positive, and 81 cases tested negative on the BTA stat test. VUC diagnosed three cases as unequivocally positive for TCC, 93 cases as negative, and four cases in which unqualified atypical urothelial cells were noted. TCC was confirmed by cystoscopy and bladder biopsy in three of three cases diagnosed by VUC and in three of 19 cases that tested positive by the BTA stat test. These findings resulted in an 84% false-positive rate for the BTA stat test and no false-positive cases for VUC during the 12-mo follow-up period. The results indicate that the sensitivity and specificity of BTA stat test are comparable to those of VUC; however, owing to a relatively high false-positive rate, it can at best act as an adjunct to urine cytological study for bladder cancer screening.     

DNA flow cytometry and bladder irrigation cytology in detection of bladder carcinoma

In this study we assessed the role of DNA flow cytometry (FCM) as an adjunct to bladder irrigation cytology to detect carcinoma of the bladder. We selected only those cases who had urinary symptoms and cystoscopic examination or histology-proven cases of bladder cancer who underwent cystoscopy for a follow-up study. Cystoscopy, cytologic examination, and DNA FCM were performed in every case. There were 9 fresh cases and 21 follow-up cases of proven transitional-cell carcinoma (TCC) of the bladder. Cystoscopy revealed growth in all 9 fresh cases as well as in 11 follow-up cases. Cytology was positive in 16 cases, out of which there were 8 each of fresh and recurrent cases. None of the cases showed positive cytology with negative cystoscopy findings. DNA FCM was positive in 13 cases. Aneuploidy was detected in 5 cases, out of which there were 3 hyperdiploid and 2 hypodiploid cases. Nine cases had high (equal or more than 10%) S and G2-M phase cells, ranging from 10-19.36%. One case showed aneuploidy along with high S-G2M phase. Both cytology and DNA FCM were positive in 9 cases. In 2 cases, DNA FCM showed aneuploidy, but cytology and cystoscopy were negative. The sensitivity and specificity of the bladder wash cytology were 80% and 100%, and those for DNA FCM were 55% and 83.3%, respectively. We conclude that both bladder wash cytology and DNA FCM techniques should be done in all the cases of suspected TCC to detect more number of positive cases.     

Does p53 immunostaining improve diagnostic accuracy in urine cytology?

The frequent change of the transitional cell carcinoma of the urinary tract accounts for the fact that cytological abnormalities in urinary specimens are often not sufficient to enable a definitive diagnosis of malignancy. The purpose of this work was to evaluate the possible use of p53 protein in increasing the diagnostic accuracy of urinary cytology. The expression of p53 was investigated by immunocytochemistry in two groups of urinary specimens, one cytologically positive and the other cytologically negative for cancer. Immunostaining was carried out using a monoclonal antibody to p53. In the positive group, in which bladder cancer was confirmed by cystoscopy and biopsy (31 cases), positive reaction for p53 was found in 55% of the cases (17 cases). In the negative group (92 cases), presence of cancer was histologically ascertained in 64 cases and in this group 15 cases (23.4%) showed positive p53 staining. In the remaining 28 cases of this group, where TCC was not present, 7 cases showed p53 positivity in non-neoplastic urothelial cells. This result shows that, while immunocytochemical detection of p53 in urinary specimens may be used for prognostic evaluation of patients with bladder cancer, it does not contribute to the diagnostic accuracy in cases with morphologically inconclusive or negative cytology. The sensitivity and specificity of the method in detecting bladder carcinoma were 23.5 and 75%, respectively. Diagn. Cytopathol. 1997;17:436–439. © 1997 Wiley-Liss, Inc.     

Suspicious urinary cytology with negative evaluation for malignancy in the diagnostic investigation of haematuria: how to follow up?

AIMS: To define the natural history of patients with suspicious urinary cytology and negative initial evaluation for malignancy in the investigation of haematuria. PATIENTS AND METHODS: Data from the hospital information support system on urinary cytology examinations carried out at one centre were audited over a period of 24 months. There were 102 patients who had suspicious urinary cytology for malignant cells with negative initial evaluation. Follow up investigations, treatment, and final outcome were noted. RESULTS: There were 102 patients with suspicious urinary cytology and negative initial evaluation for malignancy in 24 months, with a mean follow up of 15.7 months. Seventy patients had no obvious pathology on initial investigations. Forty one patients were found to have urological malignancies (29 bladder, eight ureteric, and four prostate) on follow up. All patients diagnosed as having urothelial malignancies on follow up had either persistent suspicious cytology (29) or recurrent haematuria (eight). The mean duration for appearance of lesions was 5.6 months (range, 3-12 months). Three patients had suspicious digital rectal examination and biopsies confirmed adenocarcinoma of the prostate. One patient had urinary retention and transurethral resection of prostate showed prostatic adenocarcinoma. The presence of suspicious cells on repeat urine analysis was the only significant factor in predicting the presence of urothelial tumours (p = 0.002). CONCLUSION: Patients with persistent suspicious/positive cytology or recurrent haematuria need further evaluation and follow up. Asymptomatic patients or patients with obvious benign pathology do not require repeat evaluation. Careful urological evaluation, including prostate, should be carried out in these patients.