CD44 splice variant expression in clear cell carcinoma of the ovary

Objective. CD44 is a surface glycoprotein widely distributed among differen t tissues. Malignant tumors may show a more complex pattern of CD44 express ion, indicating a loss of splice control. The aim of our study is to invest igate the expression of CD44 splice variants (CD44v) and its metastatic pot ential in clear cell carcinoma of the ovary. Methods. Twenty-two cases of clear cell carcinoma of the ovary were evaluat ed for CD44 standard form (CD44s) and splice variants: -4v, -6v, and -9v ex pression by immunocytochemistry. Results. Twenty-one primary ovarian tumors and 23 metastatic sites were ava ilable for evaluation. Eighteen of 21 (86%) of ovarian sections studied exp ressed CD44s; 15/21 (71%) expressed CD44 4v; 14/21 (67%) expressed CD44-6v; and 12/21 (57%) expressed CD44-9v. Of 23 metastatic sites evaluated, 87% e xpressed CD44s. In contrast, only 5 (22%) metastases had CD44-4v and CD44-6 v expression and 8 (35%) had CD44-9v immunoreactivity. None of 10 normal co ntralateral ovaries expressed CD44s or any splice variants. In 2 cases we h ad tumor available from the primary surgery, and subsequent recurrences. Bo th recurrences showed decreased expression of CD44-4v and CD44-6v. Conclusions. Clear cell carcinoma of the ovary shows an abnormal pattern of CD44s expression and mRNA splicing when compared to the contralateral norm al ovary in the same patient. Metastases of clear cell carcinoma show a dow nregulation in expression of some splice variants. Furthermore, we have dat a that suggest that as the tumors recur, CD44s and its isoforms are downreg ulated. Our results suggest that alternative mRNA splicing of CD44 may be i mportant in the development of metastases from clear cell carcinoma of the ovary. (C) 1998 Academic Press.