CD44 VARIANT EXPRESSION IS A COMMON FEATURE OF EPITHELIAL OVARIAN-CANCER - LACK OF ASSOCIATION WITH STANDARD PROGNOSTIC FACTORS

Purpose: CD44 is a hyaluronic acid receptor that exists as a standard 90-kd form (CD44S) as well as several CD44 variant isoforms produced t hrough alternative splicing. Expression of CD44 variants is associated with clinically aggressive behavior in some human tumors. The purpose of the present study is to define the expression of CD44 variant isof orms in ovarian cancer and to investigate whether the expression of th ese molecules is associated with adverse prognosis. Materials and Meth ods Six specimens of normal ovarian surface epithelium (NOSE) and 31 s eparate cases of newly diagnosed ovarian cancer were studied by a comb ination of reverse-transcription polymerase chain reaction (RT-PCR) an d immunoperoxidase staining. Clinical correlation wets made between CD 44 variant expression and stage (I/II v III/IV), residual disease (les s than or equal to 2.0- v > 2.0-cm mass), age (less than or equal to 6 5 v > 65 years), histology (papillary serous v other), grade, and surv ival. Results: RT-PCR analysis revealed that NOSE predominantly expres sed transcripts for CD44S, as well as a restricted pattern of transcri pts characteristic of CD44 splice variants. CD44S and CD44 variant exo n nine sequences (CD44-9v) were focally expressed in one of two NOSE s pecimens examined by immunoperoxidase staining. In comparison, the maj ority (71%) of ovarian cancer specimens expressed a complex pattern of CD44 splice variants by RT-PCR analysis. Immunoperoxidase studies rev ealed that the majority of ovarian cancer specimens expressed both CD4 4S and CD44-9v, whereas expression of sequences from variant exons 3, 4, and 6 was uncommon. There was no association between CD44 variant e xpression (transcript or protein) and stage, residual disease, age, hi stology, grade, or survival. Conclusion: Expression of CD44S and CD44- 9v is a common feature of epithelial ovarian cancer cells. The lack of a significant association between CD44 variant expression and prognos is suggests that other factors may be more important in determining th e clinical behavior of this disease. J Clin Oncol 13:1912-1921. (C) 19 95 by American Society of Clinical Oncology.