SPLICE VARIANTS OF CD44 IN HUMAN CERVICAL-CANCER STAGE IB TO IIB

Aberrant expression of the cell adhesion molecule CD44 has been detect ed in human tumors and the expression of specific CD44 isoforms (splic e variants) has been shown to be associated with metastasis and poor p rognosis in human malignancies. We used three different variant exon s equence-specific murine monoclonal antibodies to epitopes encoded by e xon v5, exon v6, or exon v7-v8 of human variant CD44 to study the expr ession of CD44 splice variants by immunohistochemistry in human cervic al cancer. One-hundred five patients with surgically treated squamous cell carcinomas of the cenix stages IB to IIB were included in the stu dy. CD44 splice variants CD44v5, CD44v6, and CD44v7-8 were detected in 70, 67, and 26%, respectively. Tumors expressing exon v6 had signific antly more often metastasized to the pelvic nodes (58 vs 79%, P = 0.04 ). Expression of exon v6 was significantly correlated with a greater p robability of vascular space invasion (73 vs 50%, P = 0.04) and a sign ificantly lower rate of inflammatory stromal reaction (48 vs 78%, P = 0.004). Patients suffering from tumors expressing splice variant CD44v 6 showed poorer overall survival (P = 0.03). In cases with negative pe lvic lymph nodes we found a poorer prognosis when tumors expressed CD4 4v6 (P = 0.01) or CD44v7-8 (P = 0.02). Among the investigated CD44 spl ice variants expression of exon v6 is the most promising prognostic ma rker in surgically treated cervical cancer. (C) 1995 Academic Press, I nc.