Expression of cytokeratin 20 redefines urothelial papillomas of the bladder

Harnden, Patricia; Mahmood, Nik Ritza Kosai Nik; Southgate, Jennifer

doi:10.1016/s0140-6736(98)05383-5

Cited by 121 publications

(83 citation statements)

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“…Harden et al (21) have already described the aberrant pattern of expression for CK20 as the presence of cytoplasmic immunostaining of urothelial cells other than superficial, umbrella cells. Ki-67 and p53 in nonneoplastic urothelium have been considered to be nonexpressed.…”

Section: Discussionmentioning

confidence: 99%

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Immunohistochemical Expression of CK20, p53, and Ki-67 as Objective Markers of Urothelial Dysplasia

et al. 2003

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Urothelial dysplasia and carcinoma in situ (CIS) are related to recurrence and progression of urothelial carcinoma. Distinguishing CIS and dysplasia from reactive atypia is often difficult on the basis of histological features alone. Cytokeratin 20 (CK20), p53, and Ki-67 are related either to neoplastic change or prognosis in urothelial proliferations. The objective of the present study was to establish the immunohistochemical pattern of these three antibodies in urothelial dysplasia and CIS. Three groups of patients were evaluated: 40 nonneoplastic urothelial samples, 50 cases with histologically incontrovertible CIS, and 30 samples with nonconclusive atypical changes (atypia of unknown significance). Monoclonal antibodies (MoAb) against CK20, p53, and Ki-67 (MIB-1) were used on paraffin-embedded samples. Nonneoplastic urothelium showed no reactivity to CK20 except for umbrella cells; p53 and Ki-67 were negative or weakly positive in <10% of basal cells. In the CIS group, 42% showed positivity for all three MoAb; 44%, for two; and 14%, only for one. CK20 was positive through the full thickness of the urothelium in 72% of cases, p53 was positive in 80% of cases, and Ki-67, in 94% of cases. In the third group, the suspected dysplastic cells showed strong positivity in scattered cells through the epithelium in 75% of cases. Aberrant CK20 expression in urothelial cells plus overexpression of p53 and Ki-67 are indicators of dysplastic change in urothelial mucosa. Thus, immunohistochemistry is a useful tool to confirm the diagnosis of CIS and could be helpful to distinguish dysplastic changes from reactive atypia.

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Section: Discussionmentioning

confidence: 99%

“…As previously reported, Ki-67 was considered positive when Ͼ10% of cells showed nuclear positive expression (9); p53 was considered positive when Ն20% of cells showed nuclear positivity (12), and CK20 expression was considered aberrant when there was cytoplasmic expression on urothelial cells other than superficial umbrella cells (21).…”

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confidence: 92%

Immunohistochemical Expression of CK20, p53, and Ki-67 as Objective Markers of Urothelial Dysplasia

et al. 2003

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“…Harnden et al have suggested that assessment of CK20 expression can be used as a predictor for recurrence rate and malignant potential in lowgrade urothelial tumors, concluding that tumors with abnormal CK20 expression were more likely to recur (6,7).…”

Section: Discussionmentioning

confidence: 99%

“…It has been suggested that the pattern of CK20 staining is a useful adjunct to morphology in the diagnosis of urothelial dysplasia (5). It has also been suggested that CK20 expression can predict malignant potential in low-grade transitional cell tumors (6), and therefore CK20 can be useful in defining treatment strategies for patients with these tumors (7).…”

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confidence: 99%

Comparison of the WHO/ISUP Classification and Cytokeratin 20 Expression in Predicting the Behavior of Low-Grade Papillary Urothelial Tumors

et al. 2001

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“…Currently, it is not possible to assess with certainty the biological behavior of these tumors based on clinical or morphological criteria alone, and as a result it is urgent to identify early and accurate biomarkers that may predict recurrence, progression, and response to treatment. Moreover, it is important to distinguish those lesions that have no significant effect on the life expectancy, as all tumorbearing patients are diagnosed with cancer, a fact that has practical and economic implications, as well as a profound psychological effect on the patient (9). To date, several prognostic markers have been identified; these include FDA-approved biomarkers (NMP22, fibrin/fibrinogen degradation product, and basement membrane components), blood group-related antigens (ABH, Lewis antigen), tumor-associated antigens (M344, 19A211, T138, DD23), proliferation antigens (Ki67 antibody, PCNA), oncogenes (c-Erb B2, Ras, c-Myc, mdm2), growth factors (epidermal growth factor, transforming growth factor-␤, fibroblast growth factor, vascular endothelial growth factor), adhesion molecules (cadherins, integrins), cytokeratins (keratin 20), and cell cycle regulatory proteins such as p53, pRb, cyclins, p15, p16, and p21 (10 -12).…”

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confidence: 99%

Proteomic Strategies to Reveal Tumor Heterogeneity among Urothelial Papillomas

Celis

Pálsdóttir

et al. 2002

Molecular & Cellular Proteomics

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Proteomics and immunohistochemistry were used to reveal tumor heterogeneity among urothelial papillomas (UPs) with the long term goal of predicting their biological potential in terms of outcome. First, we identified proteins that were deregulated in invasive fresh lesions as compared with normal urothelium, and thereafter we immunostained UPs with a panel of antibodies against some of the markers. Twenty-two major proteins showing variations of 2-fold or more in at least one-third of the invasive lesions were selected. Specific antibodies against several of the proteins were obtained, but only a few reacted positively in immunostaining. A panel consisting of antibodies against keratinocytes (CKs) 5, 13, 18, and 20 and markers of squamous metaplasia (CKs 7, 8, and 14) was used to probe normal urothelium and 30 UPs collected during a period of five years. Four UPs showed a normal phenotype, whereas the rest could be grouped in five major types that shared aberrant staining with the CK20 antibody. Type 1 heterogeneity (n ‫؍‬ 4) showed preferred staining of the umbrella cells with the CK8 antibody. Type 2 (n ‫؍‬ 11) was typified by the staining of the basal and intermediate layers with the CK20 antibody. Type 3 (n ‫؍‬ 7) was characterized by the predominant staining of the basal cell layer with the CK5 antibody. Type 4 (n ‫؍‬ 1) showed areas of CK7 negative cells, whereas type 5 (n ‫؍‬ 3) showed loss of staining of the basal cells with the CK20. 29% of the patients experienced recurrences, but none progressed to invasive disease. Patients harboring phenotypic alterations in the basal cell compartment (types 3 and 5) showed the highest number of recurrences (4/7 and 2/3, respectively), and all type 3 lesions progressed to a higher degree of dedifferentiation. Even though a long term prospective study involving a larger sample size is required to assess the biological potential of these lesions, we believe that this approach will prove instrumental for revealing early phenotypic changes in different types of cancer. Molecular & Cellular Proteomics 1:269 -279, 2002.

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Expression of cytokeratin 20 redefines urothelial papillomas of the bladder

Cited by 121 publications

References 12 publications

Immunohistochemical Expression of CK20, p53, and Ki-67 as Objective Markers of Urothelial Dysplasia

Immunohistochemical Expression of CK20, p53, and Ki-67 as Objective Markers of Urothelial Dysplasia

Comparison of the WHO/ISUP Classification and Cytokeratin 20 Expression in Predicting the Behavior of Low-Grade Papillary Urothelial Tumors

Proteomic Strategies to Reveal Tumor Heterogeneity among Urothelial Papillomas

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