Expression And Prognostic Value Of CD44 Isoforms In Nephroblastoma (Wilms Tumor)

Abstract

CD44 is a group of transmembranous glycoproteins formed by alternative splicing of a single messenger RNA. An abnormal pattern of CD44 expression has been demonstrated in several human malignancies. We evaluate the prognostic value of standard CD44 (CD44s) and some of its isoforms in treating clinical Wilms tumor. The immunohistochemical expression of CD44 isoforms was studied in paraffin material of 61 clinical Wilms tumors. Patients were treated preoperatively with chemotherapy and mean followup was 5.7 years. Generally CD44s, CD44v5 and CD44v10 were expressed in normal kidney tissues and at variable levels in the 3 cell types of Wilms tumor (blastemal, epithelial and stromal). No CD44v6 expression was found neither in normal kidney or in tumor tissue. CD44s, CD44v5 and CD44v10 epithelial expression gradually decreased from stage T1 to T3. By contrast the percentage of CD44 positive cells in the blastemal component significantly increased from T1 to T3. CD44 immunoreactive blastema cells were found in 62%, 44% and 41% for CD44s, CD44v5 and CD44v10, respectively. Blastemal expression of CD44s and CD44v5 statistically significantly correlated with clinicopathological stage. Univariate and multivariate analyses showed that blastemal CD44v5 expression was indicative of poor prognosis. Increased expression of CD44v5 in the blastemal part of Wilms tumor correlated with tumor stage, clinical progression and tumor related death. Therefore, blastemal CD44v5 expression may be of value in identifying patients with a high propensity for distant metastases. These patients might benefit from adjuvant chemotherapy and/or radiotherapy.