Abstract:Background: Differentiation of urothelial hyperplasia, dysplasia and carcinoma in situ (CIS) may pose diagnostic difficulties. We aim to evaluate the role of CK20, p53 and p63 in differentiation of such lesions. Methods: we evaluate these markers in 213 cases of bladder lesions (14 hyperplasia, 7 dysplasia, 5 CIS, 25 noninvasive and 162 invasive urothelial carcinoma) in a retrospective study on sections from formalin-fixed, paraffin-embedded blocks. Cytoplasmic staining considered for CK20 and nuclear staining… Show more
“…Out of 25 cases of LGPUC, 12 (48%) and three (12%) cases show moderate and strong nuclear positivity for p53, which is consistent with the study by Raheem et al [ 11 ]. Expression of p63 in eight cases (32%) is moderate nuclear positivity and in 15 cases (60%) was strong nuclear positivity which is similar to a study done by Ali koyuncuer [ 12 ].…”
Section: Discussionsupporting
confidence: 91%
“…Expression of p63 in eight cases (32%) is moderate nuclear positivity and in 15 cases (60%) was strong nuclear positivity which is similar to a study done by Ali koyuncuer [12]. In this study, 34 cases were included under HGPUC, out of which 28 cases (82.35%) show strong nuclear positivity for p53, which is consistent with the study done by Raheem et al [11]. HER2 plays a critical role in cell proliferation and tumorigenesis; it has been widely studied in breast cancer as a poor prognostic factor and therapeutic target.…”
Urothelial carcinomas account for the majority of all primary bladder cancers, making bladder cancer the second most frequent genitourinary malignancy after prostate cancer. Bladder cancer risk rises with age and most of them return after resection due to their multifocal distribution, and they often develop in superficial locations. Like many other cancers, bladder carcinoma is associated with a few tumor markers that have been evaluated in the past. They include p53, p63, and HER2. This study was conducted on 88 patients suspected of urinary bladder carcinoma. This prospective study was done at the Department of Pathology, Osmania General Hospital, Hyderabad from August 2017 to July 2019. Of the 88 patients, 76 were diagnosed with bladder carcinoma and the remaining 12 were non-neoplastic. The primary neoplastic lesions of the urinary bladder were predominantly seen in patients older than 40 years and were found to be statistically significant (p<0.01). Of the 34 cases of high-grade papillary urothelial carcinoma (PUC), 26 (76.47%) were males, eight cases (23.53%) were females, while among the 25 cases of low-grade PUC, 20 cases (80%) were males, and five cases (20%) were females. In seven cases of squamous cell carcinoma, six cases (85.71%) were males and only one case (14.29%) was female. Of the two cases of adenocarcinoma, male and female gender accounted for one case each (50%). The two cases of papillary urothelial neoplasm of low malignant potential were males in the study. On the whole, the primary urinary bladder lesions are more predominant in the males (77.63%) than the females (22.37%). Overexpression of p53 is negatively connected to p63 expression, and HER2 and p53 were strongly associated with high tumor grade in urothelial carcinoma.
“…Out of 25 cases of LGPUC, 12 (48%) and three (12%) cases show moderate and strong nuclear positivity for p53, which is consistent with the study by Raheem et al [ 11 ]. Expression of p63 in eight cases (32%) is moderate nuclear positivity and in 15 cases (60%) was strong nuclear positivity which is similar to a study done by Ali koyuncuer [ 12 ].…”
Section: Discussionsupporting
confidence: 91%
“…Expression of p63 in eight cases (32%) is moderate nuclear positivity and in 15 cases (60%) was strong nuclear positivity which is similar to a study done by Ali koyuncuer [12]. In this study, 34 cases were included under HGPUC, out of which 28 cases (82.35%) show strong nuclear positivity for p53, which is consistent with the study done by Raheem et al [11]. HER2 plays a critical role in cell proliferation and tumorigenesis; it has been widely studied in breast cancer as a poor prognostic factor and therapeutic target.…”
Urothelial carcinomas account for the majority of all primary bladder cancers, making bladder cancer the second most frequent genitourinary malignancy after prostate cancer. Bladder cancer risk rises with age and most of them return after resection due to their multifocal distribution, and they often develop in superficial locations. Like many other cancers, bladder carcinoma is associated with a few tumor markers that have been evaluated in the past. They include p53, p63, and HER2. This study was conducted on 88 patients suspected of urinary bladder carcinoma. This prospective study was done at the Department of Pathology, Osmania General Hospital, Hyderabad from August 2017 to July 2019. Of the 88 patients, 76 were diagnosed with bladder carcinoma and the remaining 12 were non-neoplastic. The primary neoplastic lesions of the urinary bladder were predominantly seen in patients older than 40 years and were found to be statistically significant (p<0.01). Of the 34 cases of high-grade papillary urothelial carcinoma (PUC), 26 (76.47%) were males, eight cases (23.53%) were females, while among the 25 cases of low-grade PUC, 20 cases (80%) were males, and five cases (20%) were females. In seven cases of squamous cell carcinoma, six cases (85.71%) were males and only one case (14.29%) was female. Of the two cases of adenocarcinoma, male and female gender accounted for one case each (50%). The two cases of papillary urothelial neoplasm of low malignant potential were males in the study. On the whole, the primary urinary bladder lesions are more predominant in the males (77.63%) than the females (22.37%). Overexpression of p53 is negatively connected to p63 expression, and HER2 and p53 were strongly associated with high tumor grade in urothelial carcinoma.
“…Urothelial carcinoma is the 10th most common and the second most frequent genitourinary malignancy, worldwide [35]. As urothelial carcinoma has a high recurrence rate, an early, precise differentiation of precursor neoplasms from benign reactive atypia is critical [36]. For HL patients, results were negative for all inclusion markers except Ki67 in 5 cases.…”
A precise diagnostic of precursor dysplastic urothelial lesions is critical for patients but it can be a challenge for pathologists. Multiple immunohistologic markers (panel) improve ambiguous diagnostics but results are subjective, with a high degree of observational variability. Our research objective was to evaluate how a classification algorithm may help morphology diagnostic. Data coming from 45 unequivocal cases of flat urothelial lesions (the training set: 20 carcinomas in situ, 8 dysplastic and 17 reactive lesions) were used as ground truth in training a random tree classification algorithm. 50 atypia of unknown significance diagnostics (diagnostic set) were digitally re-classified based on morphological and immunohistochemical features as possible carcinoma in situ (20), dysplastic (17) and reactive atypia cases (13). The main sorting criterium was morphologic (nuclear area). A four-markers panel was used for a precise classification (74% correctly classified, 93% accuracy, 76% precision, averaged ROC=0.828). 3 cases were false negative. The performance of the immunohistologic panel was evaluated based on a stain index, calculated for CD20, p53, Ki67 and observed for CD44. Within training set, the immunohistologic performance was high. In the diagnostic set both the percentage of high stain index for each marker and the percentage of cases with 2-3 strong markers were low, explaining the initial high number of equivocal cases. In conclusion, digital analysis of morphologic and immunohistologic features may bring clarification in classification of equivocal urothelial lesions. Computational pathology supports diagnostic process as it can measure features and handle data in a precise, reproducible and objective way. In our proof of concept study, a low number of cases and the (deliberate) absence of clinical data were main limitations. Validation of the method on a high number of cases, use of genomics and clinical data are essential for improving the reliability of machine learning classification
“…All this necessitates the search for new approaches in determining the biological behavior of urothelial malignancies and establishing new prognostic and predictive markers for these tumors. As reported by some studies, one marker showing promise in this area is the expression of Cytokeratin 20 (CK20) by the tumor cells [ 5 , 6 ].…”
Section: Introductionmentioning
confidence: 99%
“…In contrast, CK20 is expressed diffusely throughout the mucosal layer in carcinoma in situ in around 70%-80% of cases [ 5 ]. There are also conflicting reports on the potential role of CK20 as a marker used for the grading and staging of urothelial carcinoma in low-grade (G1-2) and high-grade (G2-G3) [ 6 ].…”
IntroductionSeveral clinical peculiarities mark urothelial carcinomas and their biological behavior. Key in these are its relatively indolent course before manifestation and its high recurrence rate. So far, no biomarker has been identified as a predictor for these factors. The current study aims to evaluate the role of cytokeratin 20 (CK20) in non-invasive urothelial carcinomas (pTa and pT1) of the urinary bladder and its diagnostic and predictive role in tumor staging and recurrence.
Materials and methodsThe study utilizes a retrospective, non-clinical approach via immunohistochemical marking of the paraffinembedded tumor tissues for the initial diagnosis. Expression patterns were compared with tumor grade and stage, as well as the incidence of recurrence within a five-year follow-up period.
ResultsA strong statistical correlation was established between expression and tumor grade, with high-grade tumors showing weak to moderate expression of CK20 while low-grade tumors showed an intensive expression pattern. No correlation was noted between the expression pattern, patient age and gender, tumor stage, and the likelihood of local recurrence.
ConclusionWhile CK 20 is a reliable diagnostic marker when used together with other markers, its expression pattern in our study correlated only with bladder urothelial carcinoma grade.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.