scholarly journals Evaluation of a triple combination of cytokeratin 20, p53 and CD44 for improving detection of urothelial carcinoma in urine cytology specimens

CytoJournal ◽  
2013 ◽  
Vol 10 ◽  
pp. 25 ◽  
Author(s):  
Brent Arville ◽  
Emily O’Rourke ◽  
Fai Chung ◽  
Mahul Amin ◽  
Shikha Bose

Background: Atypical urine cytology results trigger cystoscopy or molecular tests, both of which are costly, complex and difficult to perform tests. Several immunostains are being investigated to improve cancer detection; however, cytology material is limited and restricts the use of multiple immunostains. This study was designed to determine the utility of a cocktail of three stains, cytokeratin (CK20), p53 and CD44 in urine cytology samples for improving the detection of urothelial carcinoma. Materials and Methods: Urine cytology specimens with cell blocks containing adequate cytologic material between 2005 and 2010 and subsequent follow-up biopsy and/or Urovysion test (102 cases including 29 negative, 56 atypical and 17 malignant) were included in the study and evaluated with the triple stain. Results were first validated on the positive and negative cases and then applied to the atypical cases to determine the utility in the diagnosis of urothelial carcinoma. Results: Based on the validation and published literature, two distinct immunoprofiles were defined – malignant, characterized by at least five CK20 and/or p53 positive atypical cells and reactive, all other staining patterns. The malignant immunoprofile showed 88% sensitivity, 78% specificity, 74% positive predictive value (PPV) and 90% negative predictive value (NPV) for detecting urothelial carcinoma. These values improved to 95% sensitivity and 96% NPV when low-grade urothelial carcinoma cases were excluded. Summary: Our results indicate that the triple stain is an inexpensive, easy to perform test most useful for differentiating high-grade urothelial carcinoma from its mimics. However Inclusion of CD44 in the cocktail did not provide additional value and is best excluded.

CytoJournal ◽  
2020 ◽  
Vol 17 ◽  
pp. 3
Author(s):  
Song-Yi Choi ◽  
Kyung-Hee Kim ◽  
Kwang-Sun Suh ◽  
Min-Kyung Yeo

Background: Urine cytology is a noninvasive and inexpensive method; however, it is limited in low sensitivity for detecting and monitoring urothelial carcinoma (UC). To overcome limitation of cytology, several tests using urine samples have been attempted that immunocytochemical staining is an inexpensive and easy to perform ancillary technique. Dual immunocytochemical staining for p53 and cytokeratin 20 (CK20) is assessed in liquid-based urine cytology slides. Materials and Methods: Liquid-based urine cytology samples collected between 2008 and 2013 and matched follow-up biopsy samples of high-grade UC (HGUC) (n = 44) and low-grade UC (LGUC) (n = 14) were analyzed. Results: Urine cytology showing atypical cells was subjected to dual-color immunostaining for p53 and CK20. The sensitivity of urine cytology combined with p53 and CK20 immunostaining was 77.3% in HGUC and 52.9% in LGUC. Of 20 cases diagnosed with atypia by urine cytology, 13 (65%) were positive for p53 or CK20. Dual immunocytochemical staining for p53/CK20 improved the diagnostic accuracy of urine cytology. Conclusions: The present results indicate that cytomorphology combined with p53/CK20 immunostaining is useful for the detection of HGUC and LGUC.


2022 ◽  
pp. 1-8
Author(s):  
Bantita Phruttinarakorn ◽  
Sirithep Plumworasawat ◽  
Jitchai Kayankarnnavee ◽  
Jirasit Lualon ◽  
Atcharaporn Pongtippan

<b><i>Introduction:</i></b> Urothelial carcinoma is one of the most common human cancers, both in Thailand and worldwide. Urine cytology is a screening tool used to detect urothelial carcinoma. The Paris System for Reporting Urinary Cytology (TPSRUC) was first published in 2016 to standardize the procedures, reporting, and management of urothelial carcinoma. Diagnostic categories include negative for high-grade urothelial carcinoma (NHGUC), atypical urothelial cells (AUCs), suspicious for HGUC (SHGUC), HGUC, low-grade urothelial neoplasm, and other malignancies. <b><i>Material and Methods:</i></b> In a retrospective review, urine cytology specimens from 2016 to 2019 were reevaluated using the TPSRUC. The risk of high-grade malignant neoplasm (ROHM) for each diagnostic category was calculated. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of prediction of high-grade malignant neoplasms were evaluated for cases with histological follow-up specimens. <b><i>Results:</i></b> In total, 2,178 urine cytology specimens were evaluated, of which 456 cases had follow-up histological specimens. The ROHM in each diagnostic category was as follows: NHGUC, 17.4%; AUC, 49.9%; SHGUC, 81.2%; HGUC, 91.3%; and other malignant neoplasms, 87.5%. The sensitivity, specificity, PPV, NPV, and accuracy for high-grade malignant neoplasm prediction were 63%, 92.8%, 89%, 73.1%, and 78.5% when AUC was included as malignant in the comparison and 82.6%, 74.7%, 75.1%, 82.3%, and 78.5% when AUC was not considered malignant. <b><i>Conclusions:</i></b> TPSRUC provides reliable results that are reproducible by different interpreters and is a helpful tool for the detection of HGUC.


CytoJournal ◽  
2015 ◽  
Vol 12 ◽  
pp. 2 ◽  
Author(s):  
Sue Chang ◽  
Elaine Smith ◽  
Mary Levin ◽  
Jian-Yu Rao ◽  
Neda A. Moatamed

Background: Detection of urothelial carcinoma (UC) by urine cytology can be challenging. Recently, ProEx C has been studied as a marker to improve detection of UC. ProEx C is an assay targeting expression of topoisomerase IIa and minichromosome maintenance protein-2 and is currently utilized to assist in diagnoses of the gynecological specimens. In this study, we compared the utility of ProEx C and UroVysion in urine specimens. Materials and Methods: Twenty-seven urine specimens with UroVysion assay analysis and surgical biopsy follow-up were selected. The smears were stained with ProEx C. ProEx C and UroVysion assay results were separated into two categories based on surgical biopsy follow-up (benign or neoplastic). Surgical biopsy diagnoses were used as the gold standard for comparative evaluation of the two assays. The surgical follow-up was 9 benign, 2 low grade, and 16 high grade UCs. Results: The sensitivity was 88.9% for ProEx C and 55.6% for UroVysion, while the specificity was 77.8% for ProEx C and 44.4% for UroVysion. Positive predictive value was 88.9% for ProEx C and 66.7% for UroVysion. Negative predictive value was 77.8% and 33.3% for ProEx C and UroVysion, respectively. Using the two-tailed paired t-test, P value of 0.033 was obtained when ProEx C stain was compared with the UroVysion assay. Conclusion: ProEx C immunocytochemistry has a more favorable performance than fluorescent in-situ hybridization with a significant difference between the two assays using paired two-tail t-test (P = 0.0033).


CytoJournal ◽  
2016 ◽  
Vol 13 ◽  
pp. 26 ◽  
Author(s):  
Hyun-Jung Kim ◽  
Lucky Sung ◽  
Jung-Yeon Kim ◽  
Kyeongmee Park

Atypical urine cytology (CYT) triggers a cystoscopic or another ancillary investigation that targets urothelial neoplasms. We report a case presenting as an unknown primary malignancy, which illustrated the diagnostic utility of direct double immunostaining for cytokeratin 20 (CK20)/p53 expression in a urine CYT specimen. A 42-year-old woman visited the emergency room for pain in her right lower abdominal quadrant. Computed tomography revealed postrenal obstructive hydronephrosis, and her urine CYT showed malignancy, type undetermined. Atypical cells that are positive for cytoplasmic expression of CK20 and nuclear expression of p53 could facilitate the decision to perform a nephroureterectomy for urothelial carcinoma.


2005 ◽  
Vol 72 (3) ◽  
pp. 301-306
Author(s):  
M. Ciaccia ◽  
R. Bertoloni ◽  
F. Pinto ◽  
A. Calpista ◽  
P.F. Bassi

Urine cytology is a reliable and well known tool in the diagnosis and follow-up of patients with transitional cell carcinoma even if it has high sensitivity only in high grade tumors and carcinoma in situ. In order to improve sensitivity of this test in patients with low grade tumors, new methods such as cytometry, microsatellite assays, Immunocyt®, fuorescence in-situ hybridization and Thin-Prep monolayer have been developed. These new assays will be able to increase the cytology detection rate and to predict the outcome of transitional cell carcinoma.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1937-1937
Author(s):  
Xavier Leleu ◽  
Renee Leduc ◽  
Meghan Rourke ◽  
Brianna Harris ◽  
Aldo M. Roccaro ◽  
...  

Abstract Abstract 1937 Poster Board I-960 Background. Waldenstrom's macroglobulinemia is a rare B cell neoplasm characterized by the production of a monoclonal IgM protein and a lymphoplasmacytic infiltrate in the bone marrow. The clinical manifestations related to tumor infiltration include hepatomegaly (20%), splenomegaly (15%) and lymphadenopathy (15%). Organomegaly was associated with adverse prognosis in a large series of WM. More sensitive tools of tumor burden and prognosis are needed in these patients. The use of FDG-PET has not been previously studied in WM but has proved an effective diagnostic and prognostic tool in other in low-grade lymphomas. Therefore the objective of this study was to determine whether FDG-PET was an effective tool in evaluating pts with WM. Methods. We prospectively studied PET/CT in 39 WM patients homogeneously treated with bortezomib-rituximab (given IV bortezomib 1.6mg/m2 at days 1, 8, 15 q 28 days × 6 cycles and rituxan 375 mg/m2 at days 1, 8, 15, 22 on cycles 1 and 4) on a phase II clinical trial, at diagnosis (N=12) and with relapsed/refractory disease (N=27). All pts underwent staging evaluation by FDG-PET in combination with CT scan before and after therapy. PET results were analyzed as positive or negative. Response (ORR) was assessed after cycle 3, confirmed with 2 consecutive values and included minor response or better. Overall (OS) and treatment free survivals (TFS) were calculated from start of treatment to date of last follow up and time of next treatment, respectively. Results. The median age of the population was 62 years (range, 43-78), Male/Female ratio 1.64, WM-International staging score breakdown was 46% low, 23% intermediate, 31% high. Serum M-spike was 2.5g/L (0.41-4.62) with 8% patients >= 4g/L. The overall response rate was 89.7% with minor response in 13 pts and major response in 22 pts. With a median (+/-se) follow-up of 15 months (+/-1.22), death occurred in 2 patients, and the median OS was not reached with a 3-year probability of survival of 89%. The median TFS was 21 months (+/-2.09). Twenty-five (64.1%) and 13 (37.1%) patients had a positive PET before and after treatment, respectively. 11 (45.8%) patients had a negative post treatment PET which was positive before treatment, 1 (4.8%) had a positive PET after treatment while initially negative and all other patients had no change. Patients with positive PET before treatment had no clinical-biological difference (age, gender, hemoglobin level, serum beta 2-microglobulin value, platelet count, IgM spike and ISS-WM score) with other patients. A positive PET before treatment had no influence on either OS or TFS or ORR or MR. However, a normal PET after treatment, including a negative PET after treatment which initially was positive before treatment, correlated with response (p=0.04). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for a normal PET after treatment and for a negative PET after treatment while initially positive before treatment in predicting ORR were 68.7%, 100%, 100%, 23% and 52.4%, 100%, 100%, 23.1%, respectively. Although the number of deaths is low in this series, a positive PET after treatment was an adverse prognostic factor for OS. The median survival and the 2-year probability of survival was not reached and 100% for patients with a normal (negative) PET after treatment (number of death/number of pts in the group, O/N=0/22) while it was 20 months and 46% for patients with a positive PET after treatment (O/N=2/13 ), respectively (p=0.019). Conclusion: Over 60% of WM pts demonstrated FDG-avid disease when using FDG-PET scans with the majority showing negative imaging after therapy. PET positive scans after therapy correlated with poor prognosis. FDG-PET scans may prove an effective tool in the diagnosis and prognosis in WM. Disclosures: No relevant conflicts of interest to declare.


2011 ◽  
Vol 40 (9) ◽  
pp. 755-759 ◽  
Author(s):  
Ruchi Srivastava ◽  
Vinod Kumar Arora ◽  
Seema Aggarwal ◽  
Arati Bhatia ◽  
Navjeevan Singh ◽  
...  

2021 ◽  
Vol 8 ◽  
Author(s):  
An-Lun Li ◽  
Che-Yi Chou ◽  
Chien-Lung Chen ◽  
Kun-Lin Wu ◽  
Shih-Chieh Lin ◽  
...  

Urothelial carcinoma is a common urological cancer in chronic kidney disease patients. Cystoscopy and urine cytology are the clinical diagnostic tools for UC. However, cystoscopy is an invasive procedure, while urine cytology showed low sensitivity for low-grade urothelial tumors. High accuracy with non-invasive tools for UC is needed for CKD patients. Our study collected a total of 272 urine and 138 plasma samples to detect the miRNA expression levels for establishing UC signatures from CKD patients. Seventeen candidate miRNAs of biofluids were selected and confirmed by qRT-PCR. Our results showed that urinary miR-1274a and miR-30a-5p expression levels were significantly lower but miR-19a-5p expression levels were higher in UC when compared with CKD. In plasma samples, miR-155-5p, miR-19b-1-5p, miR-378, and miR-636 showed significantly lower expression in UC compared to those with CKD. The Kaplan-Meier curve showed that lower expression of miR-19a, miR-19b, miR-636 and miR-378, and higher expression of miR-708-5p were associated with poor prognosis in patients with bladder cancer. In addition, we produced classifiers for predicting UC by multiple logistic regression. The urine signature was developed with four miRNAs, and the AUC was 0.8211. Eight miRNA expression levels from both urine and plasma samples were examined, and the AUC was 0.8595. Two miRNA classifiers and the nomograms could improve the drawbacks of current UC biomarker screenings for patients with CKD.


2020 ◽  
Vol 128 (7) ◽  
pp. 460-469
Author(s):  
Ruth Montalbo ◽  
Laura Izquierdo ◽  
Mercedes Ingelmo‐Torres ◽  
Pilar Galve ◽  
Manel Solé ◽  
...  

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