CK20 versus AMACR and p53 immunostains in evaluation of Urothelial Carcinoma in Situ and Reactive Atypia

Abstract

Ancillary testing with immunohistochemistry has shown recent promise in the workup of equivocal bladder lesions. We read with interest the recent findings of Alston et al., who assessed the diagnostic utility of alpha-methylacyl-CoA racemase (AMACR) in comparison to cytokeratin 20 (CK20) in evaluation of atypia in challenging flat urothelial lesions in the differential between carcinoma in situ (CIS) and reactive atypia. AMACR was reported to be a somewhat more specific but less sensitive marker for CIS than CK20, though showing weaker intensity. Spurred by their report, with the knowledge that we had consistently and consecutively performed AMACR, CK20, and p53 on flat urothelial lesions challenging enough to reach intradepartmental consensus, we performed a retrospective review. Similarly, we found that AMACR was less sensitive (80%) and more specific (100%) than CK20, with the same caveat of less staining intensity. Additionally, our p53 review identified a significant rate (~ 27%) of equivocal/non-informative findings. Taken together, our experience in this consecutive cohort confirms the impression of Alston et al. regarding the utility and challenges of AMACR use, while highlighting challenges with p53, which we plan to use more sparingly prospectively.

The Role of Novel Bladder Cancer Diagnostic and Surveillance Biomarkers—What Should a Urologist Really Know?

“…Combined cytology and p53 was better for detecting low-grade tumors, whilst cytology and ki-67 was optimal for detecting high-grade tumors [ 148 ]. Other biomarkers proposed as an adjunct to conventional cytology such as CD20 and AMARC, CD20 and p53 or p53 combined with MCM5, MCM3 and ki67, or even dual-labeling ki67/p16, when correlated with final histology, resulted in sensitivity ranging from 80–83.5% and specificity 71.4–74.3%, not outperforming cytology alone by much [ 148 , 149 , 150 , 151 , 152 , 153 ]. CD20 performed better as the diagnostic biomarker, especially in low-grade (sensitivity 64.3 and specificity 90.0%) [ 34 , 154 , 155 ], although some Authors found discordant results and suggested cautious interpretation of positive immunohistological staining [ 155 ].…”

Diagnostic Roles of Immunohistochemical Markers CK20, CD44, AMACR, and p53 in Urothelial Carcinoma In Situ

“…Twenty-five articles were included and reviewed in this meta-analysis [ 4 , 6 , 7 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ]. From eligible studies, we collected the following information: first author’s name, publication date, study location, number of patients and IHC markers analyzed, and expression rates of uCIS and reactive/normal urothelium.…”

The Genitourinary Pathology Society Update on Classification and Grading of Flat and Papillary Urothelial Neoplasia With New Reporting Recommendations and Approach to Lesions With Mixed and Early Patterns of Neoplasia

“…Whether or not such a “basal immunophenotype” (ie, CD44/CK5 expression) has any prognostic significance in CIS requires further study. Recent evidence suggests that racemase (alpha-methylacyl-CoA racemase) and proliferation markers, such as Ki-67, may have some utility in the distinction between CIS and reactive urothelial atypia when florid examples of reactive change are studied 32–34. Finally, p53 immunohistochemistry in flat urothelial atypia can be difficult to interpret.…”

“…Finally, p53 immunohistochemistry in flat urothelial atypia can be difficult to interpret. If utilized, p53 should be evaluated with caution, recognizing that only intense nuclear reactivity in practically all lesional cells (ie, the full thickness of atypical urothelium) or a “null phenotype” should be regarded as “positive.”30,32,33…”

“…Recent evidence suggests that racemase (alpha-methylacyl-CoA racemase) and proliferation markers, such as Ki-67, may have some utility in the distinction between CIS and reactive urothelial atypia when florid examples of reactive change are studied. [32][33][34] Finally, p53 immunohistochemistry in flat urothelial atypia can be difficult to interpret. If utilized, p53 should be evaluated with caution, recognizing that only intense nuclear reactivity in practically all lesional cells (ie, the full thickness of atypical urothelium) or a "null phenotype" should be regarded as "positive."…”