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Published on: October 30, 2013
Expression of the CD44 cell adhesion molecule in urinary bladder transitional cell carcinoma
J S Ross1, A D del Rosario, H X Bui
1Department of Pathology and Laboratory Medicine, Albany Medical College, New York 12208, USA.
Insights
CD44 standard (CD44s) and CD44 variant 6 (CD44v6) expression decreases with higher grade and stage in urinary bladder cancer. Loss of CD44s correlates with abnormal DNA content, indicating its prognostic potential.
Area of Science:
- Oncology
- Molecular Biology
- Cell Adhesion
Background:
- CD44 is an integral membrane glycoprotein involved in cell adhesion and cancer progression.
- CD44 expression is noted in various human cancers but its prognostic role in bladder cancer is understudied.
Purpose of the Study:
- To investigate CD44 standard (CD44s) and CD44 variant 6 (CD44v6) expression as prognostic markers in urinary bladder transitional cell carcinoma.
- To correlate CD44 expression with tumor grade, pathologic stage, and DNA content.
Main Methods:
- Immunohistochemistry using A3D8 (for CD44s) and 2F10 (for CD44v6) monoclonal antibodies on 44 bladder transitional cell carcinoma cases.
- Qualitative and quantitative image analysis for CD44s; qualitative analysis for CD44v6.
- Comparison with tumor grade, stage, and Feulgen-stained DNA content analysis.
Main Results:
- CD44s expression significantly decreased from Grade 1 (61%) to Grade 3 (30%) tumors (P < 0.001).
- Non-invasive tumors showed higher CD44s expression (59%) than deeply invasive tumors (30%) (P < 0.001).
- Loss of CD44s staining correlated with aneuploid DNA content (P < 0.05) and aggressive tumor features (high grade/stage) for both CD44s and CD44v6 (P < 0.01).
Conclusions:
- CD44s and CD44v6 expression is progressively lost in higher-grade, higher-stage urinary bladder transitional cell carcinomas.
- CD44 expression parallels that of other cell adhesion molecules like E-cadherin, suggesting a role in tumor dedifferentiation and progression.
- CD44s and CD44v6 show potential as prognostic markers in bladder cancer.
Abstract:
CD44 cell adhesion molecule (PgP-1, ECM III, Hermes antigen) is a polymorphic integral membrane glycoprotein associated with cell matrix adhesion, lymphocyte activation, recirculation, and homing. CD44 expression has been reported in in malignant lymphoma and in a variety of epithelial human cancers but has not been studied as a prognostic marker in urinary bladder transitional cell carcinoma. CD44s (standard 85- to 95-kDa macromolecule) expression was measured by qualitative and image analysis-quantitated immunohistochemical techniques using the A3D8 monoclonal antibody. CD44v6 (a splice variant exon of CD44s) expression was measured by qualitative immunohistochemical techniques using the 2F10 monoclonal antibody. The results of CD44s and CD44v6 expression were compared with tumor grade, pathologic stage, and DNA content analysis on Feulgen-stained tissue sections in 44 cases of urinary bladder transitional cell carcinoma. The mean percentage-positive area of staining intensity for CD44s expression in Grade 1 tumors was 61%, compared with 30% for the Grade 3 tumors (P < 0.001). Non-invasive tumors featured a 59%-positive area of staining intensity, compared with the 30% staining percentage for the deeply invasive tumors (P < 0.001). There was significant correlation of aneuploid DNA content with loss of CD44s staining (P < 0.05). The staining results for CD44v6 paralleled those for the CD44s, with a significant loss of staining in high-grade and high-stage aggressive tumors in comparison with the low-grade nonaggressive tumors (P < 0.01). In urinary bladder transitional cell carcinoma, CD44s and CD44v6 expression parallels that for other cell adhesion molecules, such as E-cadherin, that feature a significant progressive loss of immunoreactivity in association with tumor dedifferentiation, advancing pathologic stage, and abnormal DNA content.
