Expression of CD44 standard and isoforms V3 and V6 in uterine smooth muscle tumors: A possible diagnostic tool for the diagnosis of leiomyosarcoma

Alterations of CD44 proteins, a family of cell adhesion molecule, have been linked with tumorigenesis, carcinogenesis, and prognosis in various neopla sms. Our aims were to evaluate and compare CD44 isoforms expression pattern s in normal myometrium, uterine leiomyomas, and leiomyosarcomas and to corr elate CD44 expression with clinicopathologic parameters. Fresh (n = 15) and formalin-fixed, paraffin-embedded (n = 76) tissues samples of myometrium, leiomyomas, and leiomyosarcomas were used for immunoblotting and immunohist ochemistry, respectively. Semiquantitative evaluation was made after immuno staining. Monoclonal antibodies were used. By immunoblotting in myometrium. and leiomyomas samples, we observed a band at 85 kd, corresponding to the apparent molecular weight of CD44s, and bands at 140 kd with the monoclonal antibodies against CD44v3 and CD44v6. In leiomyosarcomas, CD44s and CD44v6 were detected, but not CD44v3. By immunohistochemistry, decreased CD44s ex pression was found in leiomyomas and leiomyosarcomas (73.9% +/- 16.6% and 8 2.1% +/- 20.7%, respectively) compared with myometrium (97.3% +/- 6.2%; P < .0001). No CD44v6 staining was detected in myometrium, leiomyomas, and leio myosarcomas. No CD44v3 expression was detected in leiomyosarcomas, whereas myometrium and leiomyomas expressed CD44v3. For the diagnosis of leiomyosar coma, the absence of CD44v3 staining had a sensitivity, specificity, and po sitive and negative predictive values of 100%. In patients with recurrence of leiomyosarcomas, CD44s expression was decreased (P =.03). We conclude th at CD44s immunostaining in leiomyosarcomas may have prognostic significance . The loss of CD44v3 expression could be used as a putative diagnostic toot for uterine leiomyosarcomas. Hum PATHOL 32:1190-1196. Copyright (C) 2001 b y W.B. Saunders Company.