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

Arville B, O'Rourke E, Chung F, Amin M, Bose S - Cytojournal (2013)

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology, Cedars Sinai Medical Center, Los Angeles, CA, USA.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

Superficial urothelial cells highlighted by cytokeratin20 immunostain (×600)
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Figure 1: Superficial urothelial cells highlighted by cytokeratin20 immunostain (×600)

Mentions: Positive staining was noted in normal cells in variable amounts. CK20 positivity was most frequently observed in the cytoplasm of normal superficial cells identified as medium to large sized urothelial cells with rounded luminal surfaces, scalloped borders, abundant cytoplasm and often multiple nuclei. The presence of abundant cytoplasm in cells with low nuclear to cytoplasm ratio was considered as the hallmark of superficial cells [Figure 1]. p53 positivity was noted rarely in superficial cells in occasional cases while CD44 positivity was seen in some cases in basal cells identified as small cells with small round bland nuclei and scant to moderate cytoplasm. An effort was made to exclude normal cells from the interpretation of the triple stain. Results of the staining pattern noted only in morphologically atypical urothelial cells were recorded. Atypical morphology was defined as urothelial cells displaying increased nuclear to cytoplasmic ratios, nuclear hyperchromasia, coarse chromatin and/or irregular nuclear contours. Results are summarized in Table 1.


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

Arville B, O'Rourke E, Chung F, Amin M, Bose S - Cytojournal (2013)

Superficial urothelial cells highlighted by cytokeratin20 immunostain (×600)
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3927070&req=5

Figure 1: Superficial urothelial cells highlighted by cytokeratin20 immunostain (×600)
Mentions: Positive staining was noted in normal cells in variable amounts. CK20 positivity was most frequently observed in the cytoplasm of normal superficial cells identified as medium to large sized urothelial cells with rounded luminal surfaces, scalloped borders, abundant cytoplasm and often multiple nuclei. The presence of abundant cytoplasm in cells with low nuclear to cytoplasm ratio was considered as the hallmark of superficial cells [Figure 1]. p53 positivity was noted rarely in superficial cells in occasional cases while CD44 positivity was seen in some cases in basal cells identified as small cells with small round bland nuclei and scant to moderate cytoplasm. An effort was made to exclude normal cells from the interpretation of the triple stain. Results of the staining pattern noted only in morphologically atypical urothelial cells were recorded. Atypical morphology was defined as urothelial cells displaying increased nuclear to cytoplasmic ratios, nuclear hyperchromasia, coarse chromatin and/or irregular nuclear contours. Results are summarized in Table 1.

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology, Cedars Sinai Medical Center, Los Angeles, CA, USA.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus