scholarly journals Investigation of the Relationship Between the Degree of Peritumoral Brain Edema and Pathological Features of Glioma Before Surgery

2021 ◽  
Vol 18 (3) ◽  
Author(s):  
Zhenhua Wang ◽  
Xinlan Xiao
Keyword(s):  
Brain Edema ◽  
Malignant Tumors ◽  
Multivariate Logistic Regression Analysis ◽  
Expression Level ◽  
World Health ◽  
Low Grade ◽  
Ki 67 ◽  
Mutation Status ◽  
Significant Difference ◽  
Peritumoral Brain Edema

Background: Gliomas are the most common malignant tumors of the central nervous system (CNS). Preoperative prediction of the malignancy grade of gliomas are of particular importance. These tumors are often accompanied by peritumoral brain edema (PTBE). Previous studies have suggested that the degree of PTBE is an independent indicator of the prognosis of gliomas. Objectives: This study aimed to investigate the relationships between the degree of PTBE and the grade of glioma, isocitrate dehydrogenase 1 (IDH1) mutation status, and Ki-67 expression level in gliomas. Patients and Methods: In this retrospective cross-sectional study, a total of 82 patients were enrolled, according to the 2016 World Health Organization (WHO) classification of CNS tumors. Overall, 29 tumors were pathologically confirmed as low-grade gliomas (LGGs , grade I-II), whereas the remaining 53 tumors were classified as high-grade gliomas (HGGs, grade III-IV). The IDH1 mutations, Ki-67 expression, and magnetic resonance imaging (MRI) findings were retrospectively analyzed. The tumor and tumor + PTBE volumes were also measured, and the tumor edema index (EI) was calculated for each patient. Edema was then graded and correlated with the pathological parameters. Results: The degree of EI was higher in the HGG group compared to the LGG group, and the difference was statistically significant (z = -7.018, P < 0.05). Besides, the degree of EI was higher in the IDH1 wild-type compared with mutant groups (z = -4.116, P < 0.05). The degree of EI significantly associated with Ki-67 expression and patient’s age (P < 0.05), whereas there was no significant association between the degree of EI and gender (z = -0.497, P = 0.619). The Spearman’s correlation test revealed that the EI degree was positively correlated with the Ki-67 expression level and age, with correlation coefficients of 0.740 and 0.466, respectively. Moreover, the multivariate logistic regression analysis indicated that EI and IDH1 had significant effects on differentiating LGGs from HGGs (P < 0.05 for both). The receiver operating characteristic (ROC) curve analysis showed that EI was an optimal index for differentiating LGGs from HGGs, with an area under curve (AUC) of 0.822 (cutoff value: 1.722, sensitivity: 95.8%, specificity: 70.0%, 95% CI: 0.718 - 0.899). Conclusion: The degree of PTBE was found to be a valuable index for the differential diagnosis of LGGs from HGGs. It has a significant difference between IDH1 wild and mutation status, furthermore, it was positively correlated with the age and Ki-67 level.

scholarly journals Ki-67 immunostaining in astrocytomas: Association with histopathological grade – A South Indian study

2016 ◽  
Vol 7 (04) ◽  
pp. 510-514 ◽  
Author(s):  
Nandish Vastrad Shivaprasad ◽  
Suchitha Satish ◽  
Sunila Ravishankar ◽  
Manjunath Gubbi Vimalambike
Keyword(s):  
Biological Marker ◽  
World Health ◽  
Histopathological Diagnosis ◽  
Low Grade ◽  
Ki 67 ◽  
Histopathological Grade ◽  
South Indian ◽  
Significant Difference ◽  
Grade Ii ◽  
Histopathological Grading

ABSTRACT Background: Astrocytomas are the most common primary tumor of the central nervous system. The distinction between different tumor grades can be tested despite criteria given by the World Health Organization (WHO). Ki-67 is a potent biological marker used in grading of astrocytomas, which estimates growth of the neoplasm quantitatively and will help in predicting prognosis accurately. Objectives: The aim of this was to study the proliferative activity using Ki-67 immunostaining and to assess the relationship of Ki-67 staining with the histopathological grading of astrocytomas. Patients and Methods: Thirty cases of histologically proven astrocytomas were studied. The histopathological grade was assessed using the 2007 WHO criteria. Immunohistochemistry for Ki-67 was done on paraffin-embedded wax sections. P < 0.05 was considered statistically significant. Results: Thirty cases of astrocytomas studied showed a male preponderance (M:F = 1.72:1) with a mean age of 48.1 years. Of these, Grade I, (n = 1, 3.33%), Grade II, (n = 7, 23.3%), Grade III (n = 6, 20%), and Grade IV (n = 16, 53.3%) astrocytomas were analyzed. The mean Ki-67 labeling index (LI) in Grades I, II, III, and IV was 0.02, 0.81, 9.14, and 17.81, respectively. Statistically significant difference was seen in the Ki-67 LI of low-grade (Grade II) and high-grade astrocytomas (Grades III and IV). There was concordance between histopathological grading and Ki-67 LI in 27 (90%) and discordance in 3 (10%) cases. Conclusion: Ki-67 LI varies considerably in different grades of astrocytomas and considerable overlaps can be observed between them. It can be of great help in situations where there is a lack of correlation between clinical parameters and histopathological diagnosis. Determination of Ki-67 LI should constitute a part of routine investigations in patients with astrocytomas.

scholarly journals Mixed adenoneuroendocrine carcinoma of the hepatic bile duct: a case report and review of the literature

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Sulai Liu ◽  
Zhendong Zhong ◽  
Meng Xiao ◽  
Yinghui Song ◽  
Youye Zhu ◽  
...  
Keyword(s):  
Bile Duct ◽  
Neuroendocrine Tumors ◽  
Radical Surgery ◽  
Malignant Tumors ◽  
World Health ◽  
Ki 67 ◽  
Mixed Adenoneuroendocrine Carcinoma ◽  
Hilar Bile Duct ◽  
Hilar Tumor

Abstract Background The World Health Organization's updated classification of digestive system neuroendocrine tumors in 2010 first proposed the classification of mixed adenoneuroendocrine carcinoma (MANEC). The incidence of biliary malignant tumors with neuroendocrine tumors accounts for less than 1% of all neuroendocrine tumors. Moreover, the incidence of hilar bile duct with MANEC is very rare. Case presentation A 65-year-old female patient came to our hospital for repeated abdominal pain for more than 4 months and skin sclera yellow staining for 1 week. Contrast-enhanced computed tomography imaging and magnetic resonance results suggested a hilar tumor for Bismuth-Corlette Type II. The patient underwent radical surgery for hilar cholangiocarcinoma. Finally, the patient was diagnosed with hilar bile duct MANEC, staged 1 (pT1N0M0) based on the eighth edition of the AJCC. Histopathology showed that the tumor was a biliary tumor with both adenocarcinoma and neuroendocrine carcinoma. No evidence of recurrence and metastasis after 20 months of follow-up. Conclusions We first reported a MANEC that originated in the hilar bile duct. As far as we known, there were few reports of biliary MANEC, and the overall prognosis was poor. We also found that the higher the Ki-67 index, the worse the prognosis of this type of patient. Radical surgery is the most effective treatment.

Number of Nucleoli and Nucleolar Organizer Regions per Nucleus and Nucleolus — Prognostic Value in Canine Mammary Tumors

1996 ◽  
Vol 33 (5) ◽  
pp. 527-532 ◽  
Author(s):  
M. BratuliĆ ◽  
Ž GrabareviĆ ◽  
B. ArtukoviĆ ◽  
D. Capak
Keyword(s):  
Malignant Tumors ◽  
Organizer Region ◽  
Nucleolar Organizer Region ◽  
Nucleolar Organizer ◽  
Staining Technique ◽  
Mammary Tumors ◽  
World Health ◽  
Nucleolar Organizer Regions ◽  
Canine Mammary Tumors ◽  
Significant Difference

Twenty-eight canine mammary tumors were evaluated for histopathologic classification as recommended by the World Health Organization and silver-binding nucleolar organizer region (AgNOR) and nucleolus counts. Samples of surgically excised tumors and tumors taken at necropsy were fixed in neutral formalin, embedded in paraffin, and cut into 1-3-μm-thick sections. Two sections were taken from each tumor: one was stained with hematoxylin and eosin and the other was treated with the silver staining technique for the demonstration of AgNORs. After histopathologic classification, the number of nucleoli and the number of AgNORs/nucleus and AgNORs/nucleolus were determined. Statistical analysis (Student's t-test) showed a significant difference in the mean number of nucleoli ( P < 0.005), mean number of AgNORs/nucleolus ( P < 0.001), and mean number of AgNORs/nucleus ( P < 0.005) between benign and malignant canine mammary tumors. There was no significant differences between metastatic and nonmetastatic malignant tumors.

scholarly journals Analysis of Prognostic Factors of World Health Organization Grade Ⅲ Meningiomas

2020 ◽  
Vol 10 ◽  
Author(s):  
Weidong Tian ◽  
Jingdian Liu ◽  
Kai Zhao ◽  
Junwen Wang ◽  
Wei Jiang ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Cox Regression ◽  
Postoperative Radiotherapy ◽  
World Health ◽  
Low Grade ◽  
Ki 67 ◽  
Who Grade ◽  
Who Grade Iii ◽  
Grade Iii

ObjectiveWHO grade III meningiomas are highly aggressive and lethal. However, there is a paucity of clinical information because of a low incidence rate, and little is known for prognostic factors. The aim of this work is to analyze clinical characteristics and prognosis in patients diagnosed as WHO grade III meningiomas.Methods36 patients with WHO grade III meningiomas were enrolled in this study. Data on gender, age, clinical presentation, preoperative Karnofsky Performance Status (KPS), histopathologic features, tumor size, location, radiologic findings, postoperative radiotherapy (RT), surgical treatment, and prognosis were retrospectively analyzed. Progression-free survival (PFS) and overall survival (OS) were evaluated using the Kaplan-Meier method. Univariate and multivariate analysis were conducted by the Cox regression model.ResultsMedian PFS is 20 months and median OS is 36 months in 36 patients with WHO grade III meningiomas. Patients with secondary tumors which transformed from low grade meningomas had lower PFS (p=0.0014) compared with primary group. Multivariate analysis revealed that tumors location (PFS, p=0.016; OS, p=0.013), Ki-67 index (PFS, p=0.004; OS, p&lt;0.001) and postoperative radiotherapy (PFS, p=0.006; OS, p&lt;0.001) were associated with prognosis.ConclusionWHO grade III meningiomas which progressed from low grade meningiomas were more prone to have recurrences or progression. Tumors location and Ki-67 index can be employed to predict patient outcomes. Adjuvant radiotherapy after surgery can significantly improve patient prognosis.

Expression of GRP78 protein in pancreatic ductal adenocarcinoma and intraductal papillary mucinous neoplasm.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 323-323
Author(s):  
Asha R. Dhanarajan ◽  
Reginald Hill ◽  
Sam G. Pappas ◽  
Gerard J. Abood ◽  
Jennifer Lynn Gnerlich ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Intraductal Papillary Mucinous Neoplasm ◽  
Protein Quality ◽  
Expression Level ◽  
Ductal Adenocarcinoma ◽  
Pancreatic Ducts ◽  
Low Grade ◽  
Ductal Cells ◽  
Mucinous Neoplasm ◽  
Significant Difference

323 Background: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis due to late detection, aggressive biology and resistance to chemotherapy. Markers for early detection of PDAC and mediators of chemoresistance are poorly understood. GRP78 is a major endoplasmic reticulum (ER) chaperone protein critical for protein quality control of the ER. Increased GRP78 expression promotes in vitro cancer cell survival, progression, and chemoresistance. This study aims to examine expression of GRP78 protein in PDAC and intraductal papillary mucinous neoplasm (IPMN) compared to normal pancreatic ducts using immunohistochemistry (IHC). Methods: The expression of GRP78 was assessed using IHC in 93 sections of formalin-fixed paraffin-embedded tissue: normal ducts (38), low grade IPMN (IPMN-LG, 26), high grade IPMN (IPMN-HG, 9), and PDAC (20). Immunostaining intensity of GRP78 protein was categorized as no or weak staining (0-1+) and strong staining (2-3+). Fisher’s exact test with two tails was performed using the GraphPad statistical software. Results: GRP78 expression was identified in the cytoplasm of normal pancreatic ducts, IPMN and PDAC with a fine granular pattern. All PDAC and IPMN-HG showed strong expression of GRP78 while the normal ductal cells showed only minimal expression of GRP78. 73% of IPMN-LG expresses GRP78 strongly. Statistical analysis revealed a significant difference in GRP78 expression level between normal ductal cells and all three pathological conditions including PDCA, IPMN-HG and IPMN-LG (all p < 0.0001). Conclusions: This study shows that the expression level of GRP78 is significantly increased in PDAC, IPMN-HG and IPMN-LG compared to normal ductal cells. There appears to be a progressive increase in GRP78 expression from IPMN-LG to IPMN-HG and invasive PDAC. Increased GRP78 expression may be a marker for those at risk of developing PDAC. Changes in GRP78 expression over time and its role in PDAC chemoresistance should be further assessed. [Table: see text]

scholarly journals The Expressions of Wnt/β-catenin Pathway-Related Components in Brainstem Gliomas

2013 ◽  
Vol 40 (3) ◽  
pp. 355-360 ◽  
Author(s):  
Wenhao Wu ◽  
Yongji Tian ◽  
Hong Wan ◽  
Yongmei Song ◽  
Junhua Li ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Clinicopathological Characteristics ◽  
Current Treatment ◽  
Brainstem Glioma ◽  
Low Grade ◽  
Normal Brain ◽  
Ki 67 ◽  
Significant Difference ◽  
The Relationship ◽  
Brain Tissues

Background:The overall prognosis of brainstem gliomas is very poor, and the current treatment cannot significantly prolong the overall survival of these patients; therefore, studying the molecular biological mechanisms of the occurrence and development of brainstem gliomas has important significance for their treatment. The Wnt/β-catenin signaling pathway is closely associated with the occurrence and development of tumors, but its relationship with brainstem gliomas remains unclear.Methods:This study used Western blot and immunohistochemistry methods to detect the expressions of Wnt/β-catenin signaling pathway-related components such as Wnt-1, Wnt-2, β-catenin and C-myc in six cases of normal brain tissues and 24 cases of brainstem gliomas and analyzed the relationship between their expressions and clinicopathological characteristics.Results:Wnt-1 had no obvious expression in normal brain tissues and did not show any significant difference between high- and low-grade brainstem gliomas; the expressions of Wnt-2, β-catenin and C-myc in high-grade brainstem gliomas were significantly higher than that in low-grade brainstem gliomas and normal brain tissues and were positively correlated with the expression of Ki-67. Moreover, the expressions of Wnt-2 and C-myc were significantly associated with the prognosis of brainstem glioma patients; additionally, there was a trend toward increased β-catenin expression with shorter survival, but there was no statistical difference.Conclusions:Wnt/β-catenin signaling pathway might be abnormally activated and plays an important role in the occurrence and development of brainstem gliomas. Wnt-2, β-catenin and C-myc may be potential targets for brainstem glioma treatment.

scholarly journals Large Malignant Phyllodes Tumor of the Breast: Case Report of a Young Female and Review of Literature

2020 ◽  
pp. 137-146
Author(s):  
Melissa Kyriakos Saad ◽  
Imad El Hajj ◽  
Elias Saikaly
Keyword(s):  
Malignant Tumors ◽  
Pectoralis Major Muscle ◽  
Phyllodes Tumor ◽  
World Health ◽  
Low Grade ◽  
Accurate Identification ◽  
Malignant Phyllodes Tumor ◽  
Phyllodes Tumors ◽  
Post Surgery ◽  
The Right

Background: Phyllodes tumors are rare fibroepithelial neoplasm of the breast, representing 0.3 to 0.5% of all female breast neoplasms. The term ‘‘phyllodes tumor” by the World Health Organization (WHO) categorizes it into benign, borderline, and malignant tumors based on histopathological characteristics. Malignant phyllodes tumor is an uncommon but aggressive breast malignancy and accounts for approximately 25% of all phyllodes tumors.Case Presentation: A 23-year-old female patient Gravida 0 Para 0, previously healthy, with no family history of breast or ovarian cancer was referred to our institution for managing a right breast mass increasing in size over a period of 1 month associated with reddish-brown discoloration of the skin. Breast ultrasound showed an isodense oval mass measuring approximately 16x14x12cm in the right lower outer quadrant of her breast. Core biopsy and FNA done revealed a low grade phyllodes tumor. MRI of breasts showed a huge mass of the right breast occupying all quadrants, measuring 15x14.5 cm in its greatest axis with involvement of the pectoralis major muscle, with no evidence of suspicious axillary lymphadenopathy. Distant metastatic work-up with CT scan of chest abdomen and pelvis and a PET scan did not show distant metastasis. Hence, the patient underwent right total mastectomy with a final pathology compatible with malignant phyllodes tumor. She is on regular follow up and 18 months post-surgery is still disease free.Conclusion: Management of malignant phyllodes tumor remains debatable, especially when it comes to the effect of adjuvant radiotherapy and chemotherapy. From a surgical perspective, whether phyllodes tumors should be considered as epithelial breast cancers or as soft tissue sarcoma is another debate. On the other hand, although challenging, accurate identification of phyllodes tumor initially may aid in decreased recurrence.

scholarly journals Factors Associated With Dysfunction of Glymphatic System in Patients With Glioma

2021 ◽  
Vol 11 ◽  
Author(s):  
Cheng Hong Toh ◽  
Tiing Yee Siow
Keyword(s):  
Brain Edema ◽  
Diffusion Tensor ◽  
Tumor Grade ◽  
Wild Type ◽  
Mutation Status ◽  
Factors Associated ◽  
Edema Volume ◽  
Peritumoral Brain Edema ◽  
Grade Ii ◽  
The Alps

ObjectivesRodent experiments have provided some insights into the changes of glymphatic function associated with glioma growth. The diffusion tensor image analysis along the perivascular space (DTI-ALPS) method offers an opportunity for the noninvasive investigation of the glymphatic system in patients with glioma. We aimed to investigate the factors associated with glymphatic function changes in patients with glioma.Materials and MethodsA total of 201 glioma patients (mean age = 47.4 years, 116 men; 86 grade II, 52 grade III, and 63 grade IV) who had preoperative diffusion tensor imaging for calculation of the ALPS index were retrospectively included. Information collected from each patient included sex, age, tumor grade, isocitrate dehydrogenase 1 (IDH1) mutation status, peritumoral brain edema volume, tumor volume, and ALPS index. Group differences in the ALPS index according to sex, tumor grade, and IDH1 mutation status were assessed using analysis of covariance with age adjustment. Linear regression analyses were performed to identify the factors associated with the ALPS index.ResultsGroup comparisons revealed that the ALPS index of grade II/III gliomas was significantly higher than that of grade IV gliomas (p &lt; 0.001). The ALPS index of IDH1 mutant gliomas was significantly higher than that of IDH1 wild-type gliomas (p &lt; 0.001). On multivariable linear regression analysis, IDH1 mutation (β = 0.308, p &lt; 0.001) and peritumoral brain edema volume (β = −0.353, p &lt; 0.001) were the two independent factors associated with the ALPS index.ConclusionIDH1 wild-type gliomas and gliomas with larger peritumoral brain edema volumes were associated with a lower ALPS index, which may reflect impaired glymphatic function.

scholarly journals The Relationship Between Peritumoral Brain Edema and the Expression of Vascular Endothelial Growth Factor in Vestibular Schwannoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Hong-Hai You ◽  
Xiao-Yong Chen ◽  
Jin-Yuan Chen ◽  
Yue Bai ◽  
Fu-Xiang Chen
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Brain Edema ◽  
Vestibular Schwannoma ◽  
Expression Level ◽  
Vascular Endothelial ◽  
Vegf Expression ◽  
Close Relationship ◽  
Peritumoral Brain Edema ◽  
Endothelial Growth Factor

Objective: This study aimed to explore the potential mechanism of peritumoral brain edema (PTBE) formation in vestibular schwannoma (VS) by detecting intra-tumoral vascular endothelial growth factor (VEGF) expression.Methods: Between January 2018 and May 2021, 15 patients with PTBE and 25 patients without PTBE were included in the analysis. All patients enrolled in our study underwent surgery in our institution. Expression level of VEGF and microvessel density (MVD) between the two groups were analyzed. Edema index (EI) of each patient with PTBE was calculated.Results: In the PTBE group, the average of EI was 1.53 ± 0.22. VEGF expression levels were significantly enhanced in the PTBE group compared with the non-PTBE group (p &lt; 0.001). The expression level of VEGF in the PTBE group and non-PTBE group was 1.14 ± 0.21 and 0.52 ± 0.09, respectively. Similarly, there were significantly different amounts of MVD in the two groups (p &lt; 0.001). The amount of MVD in the PTBE group and non-PTBE group was 11.33 ± 1.59 and 6.28 ± 1.77, respectively. Correlation analysis showed a highly significant positive correlation between VEGF and MVD (r = 0.883, p &lt; 0.001) and VEGF and EI (r = 0.876, p &lt; 0.001).Conclusion: Our study confirmed the close relationship among VEGF expression, tumor angiogenesis, and formation of PTBE in VS patients. It may be possible to develop new effective therapies to attenuate PTBE in VS for alleviation of symptoms and reduction of postoperative complication.

Correlation of Ki-67 and p53 With the New World Health Organization/International Society of Urological Pathology Classification System for Urothelial Neoplasia

2001 ◽  
Vol 125 (5) ◽  
pp. 646-651 ◽  
Author(s):  
Stephen J. Cina ◽  
Kristen J. Lancaster-Weiss ◽  
Kristen Lecksell ◽  
Jonathan I. Epstein
Keyword(s):  
Papillary Carcinoma ◽  
World Health ◽  
Low Grade ◽  
High Grade ◽  
Ki 67 ◽  
Papillary Lesions ◽  
Flat Lesions ◽  
Papillary Hyperplasia ◽  
Health Organization ◽  
Papillary Neoplasm

Abstract Objective.—The present study examines p53 and Ki-67 staining patterns of the diagnostic entities included within the new World Health Organization/International Society of Urological Pathology (WHO/ISUP) classification of urothelial neoplasms. Design.—We retrospectively studied 151 bladder biopsies from 81 patients with the following neoplasms: normal urothelium (n = 34 biopsies); low-grade intraurothelial neoplasia (LGIUN; n = 19); high-grade intraurothelial neoplasia (HGIUN; n = 20); papillary hyperplasia (n = 4); papilloma (n = 3); papillary neoplasm of low malignant potential (LMP; n = 12); low-grade papillary carcinoma (n = 28); and high-grade papillary carcinoma (n = 31). Sections were labeled immunohistochemically with antibodies to p53 and Ki-67 (MIB-1). Two hundred cells from each lesion were visually counted, and the percentage of positive cells was tabulated without knowledge of the WHO/ISUP diagnosis. Results.—In flat lesions, p53 positivity was of limited diagnostic utility; the marker was present in 6 of 34 benign biopsies, 6 of 19 LGIUNs, and 10 of 20 HGIUNs. In one case in which HGIUN was present elsewhere in the bladder, 29% of the benign urothelial cells were p53 positive. In papillary lesions, p53 positivity was not seen in 4 of 4 cases of papillary hyperplasia, 3 of 3 papillomas, and 8 of 12 LMP tumors. In contrast, p53 was detected in 18 of 28 low-grade and 26 of 31 high-grade papillary urothelial carcinomas. A p53 labeling index (LI) greater than 30% was only seen in HGIUNs and high-grade papillary carcinomas. In flat lesions, an increased Ki-67 LI separated out benign urothelium (mean LI, 0.62%) from dysplasia (mean LI, 3.3%) and HGIUN (mean LI, 11.6%). In papillary lesions, Ki-67 positivity was as follows: papillary hyperplasia (mean LI, 1.1%); papilloma (mean LI, 4.3%); LMP tumors (mean LI, 2.5%), low-grade papillary carcinoma (mean LI, 7.3%); and high-grade carcinoma (mean LI, 15.7%). A Ki-67 LI greater than 10% was seen only in low- and high-grade papillary carcinomas, HGIUN, and single cases of LGIUN and papillary neoplasm of LMP. Conclusions.—An increased proliferative index as demonstrated by immunohistochemical staining for Ki-67 (MIB-1) is most often seen in papillary carcinoma and HGIUN. Marked p53 positivity is also characteristic of carcinoma but may be seen in benign-appearing urothelium, suggesting a “field effect” with occult molecular aberration.

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