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

Abstract

Background and Objectives: This study aimed to evaluate the diagnostic roles of various immunohistochemical (IHC) markers in urothelial carcinoma in situ (uCIS) through a meta-analysis and review of diagnostic test accuracy. Materials and Methods: The IHC markers CK20, CD44, AMACR, and p53 were evaluated in the present study. We analyzed the expression rates of the IHC markers and compared their diagnostic accuracies. Results: The estimated expression rates were 0.803 (95% confidence interval [CI]: 0.726–0.862), 0.142 (95% CI: 0.033–0.449), 0.824 (95% CI: 0.720–0.895), and 0.600 (95% CI: 0.510–0.683) for CK20, CD44, AMACR, and p53, respectively. In the comparison between uCIS and reactive/normal urothelium, the expression of CK20, AMACR, and p53 in uCIS was significantly higher than in reactive/normal urothelium. CD44 showed significantly lower expression in uCIS than in the reactive/normal urothelium. Among the markers, AMACR had the highest sensitivity, specificity, and diagnostic odds ratio. The AUC on SROC was the highest for CK20. Conclusions: In conclusion, IHC markers, such as CK20, CD44, AMACR, and p53, can be useful in differentiating uCIS from reactive/normal urothelium.

Expression of Basal Compartment and Superficial Markers in Upper Tract Urothelial Carcinoma Associated with Balkan Endemic Nephropathy, a Worldwide Disease

“…In the urothelium, the transition from basal to terminally differentiated superficial cells is reflected in the different protein synthesis for each layer, which leads to the various morphological and antigenic characteristics [11,16]. CD44 is a cell adhesion molecule involved in tumor growth and biological behavior.…”

“…CD44 realizes its functions through Fas inhibition, activating the mitogen-activated protein kinase (MAPK), and signaling and regulating the matrix metalloproteinases (MMPs) [17][18][19][20]. Recent data suggested that CD44 and p53 are important markers for the differential diagnosis of CIS from reactive/normal urothelium [11]. Inactivation of p53 results in overexpression of CD44, which may act as a tumor-promoting agent.…”

“…CK20 immunoreactivity was classified as normal (N) group (expression in superficial cells or absent staining) and altered (A) group (focal pattern or diffuse pattern, in which more than 10% of tumor cells were positive) [11]. CK5/6 was classified as normal (N) group (no staining or staining only in basal/parabasal cells) and altered (A) group (moderate to strong staining usually through the full thickness of the urothelium) [7].…”

“…The CD44 normal (N) group included strong expression on the plasma membranes of basal cells or the immunoreactivity of CD44 in basal, suprabasal, and intermediate cells, but not in the superficial cells (accentuated pattern). The altered (A) group included tumors which displayed a focal or total loss of basal CD44 expression or a focal loss of staining in an otherwise-accentuated pattern [11].…”

“…CD44 is a transmembrane glycoprotein involved in all essential cellular processes, like survival, differentiation, proliferation, migration, angiogenesis, and cellular signaling, through the presentation of cytokines and growth factors to the corresponding receptors. CD44 expression is associated with bladder cancer aggressiveness and resistance to chemo and radio treatment, and the ratio in urothelial cancer tissue and urinary exfoliated cells showed a significant correlation in the same patients; therefore, it was proposed as a prognostic predictor [9,11,12].…”