THE EXPRESSION PATTERNS OF STANDARD AND VARIANT CD44 MOLECULES IN NORMAL UTERINE CERVIX AND CERVICAL-CANCER

CD44 is a cell-surface glycoprotein postulated to play a role in tumor -cell metastasis. We have examined the expression of the standard CD44 (CD44s), and alternative spliced variants of CD44 containing variant exons v6, v9, and v10 (CD44v6, CD44v9, and CD44v10 respectively) in 9 samples of normal cervix, 6 samples of cervical intraepithelial neopla sia (GIN), and II samples with invasive cervical carcinomas. RT/PCR de monstrated the presence of CD44s in all samples of normal cervix and t hose with invasive carcinomas. CD44v6 was also found in all normal cer vical samples and in 9 tissue samples of invasive carcinomas. The resu lts also suggested that some tumor specimens had several higher molecu lar transcripts containing exon v6 compared to specimens of normal cer vix. Immunohistochemistry detected the presence of CD44s and the; abse nce of CD44v10 in both epithelial and stromal cells in all specimens. In contrast, CD44v6 and CD44v9 were stained positive in epithelial cel ls but were absent in stromal cells. The intensity of CD44v6 and CD44v 9 staining was strongest in normal cervical epithelium followed by GIN , invasive squamous cell carcinoma, and adenocarcinoma In the malignan t samples, heterogeneity in staining intensity among different cluster s of tumor cells was observed. Furthermore, poorly differentiated and undifferentiated carcinomas from patients having poor prognosis did no t stain at ah. This study suggests that variant CD44 molecules may ser ve an important function in the cell contact of cervical epithelial ce lls, and that cervical epithelium acquires heterogeneity in the expres sion of CD44 adhesion molecules during carcinogenesis, which may be re lated to tumor metastasis. (C) 1997 Academic Press