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Clear cell carcinoma of the ovary: characterization of its CD44 isoform repertoire
I Sancho-Torres1, C Mesonero, J L Miller Watelet
1Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Rochester, New York, 14642, USA.
Objective:
CD44 is a cell surface receptor implicated in tumor metastases. We have previously shown that there is a loss of CD44 splice control in clear cell carcinoma (CCCa) of the ovary. Our aim is to characterize the expression of CD44-3v, -5v, -7v, and -10v in clear cell ovarian tumors and to determine their prognostic value.
Methods:
Twenty-two cases of ovarian CCCa were studied for CD44-3v, -5v, -7v, and -10v expression by immunocytochemistry.
Results:
The primary tumors showed expression of CD44-3v, -5v, -7v, and -10v in 44, 55, 61, and 39% of the cases, respectively. We were able to compare the expression of CD44 in the primary tumor and metastatic sites from the same patient in 7 cases (metastatic sites n = 16). We observed decreased immunoreactivity of CD44-3v, -5v, -7v, and -10v in 67, 100, 93, and 92% of the sites, respectively. CD44-3v and -10v expression was absent in 100% of the nonaffected contralateral ovaries while -7v and -10v were expressed in 1/11 (9%) of them. When CD44-10v was not expressed in the primary tumor, only 18% of the women recurred or died of disease; in contrast, of the cases where it was present, 71% of the women recurred or died of disease (P = 0.049).
Conclusions:
There is aberrant alternative mRNA splicing in the development of CCCa of the ovary when compared to the contralateral nonaffected ovary. The expression of CD44-10v correlates with survival. Larger series are needed to further understand the role of CD44 isoforms in ovarian cancer metastases.
Insights
Aberrant splicing of CD44 variants, specifically CD44-10v, is observed in ovarian clear cell carcinoma (CCCa). Loss of CD44-10v expression in primary tumors correlates with improved patient survival, suggesting its prognostic value in CCCa.
Area of Science:
- Oncology
- Molecular Biology
- Gynecologic Pathology
Background:
- CD44 is a cell surface receptor critical for tumor metastasis.
- Previous research indicated a loss of CD44 splice control in ovarian clear cell carcinoma (CCCa).
- Aberrant alternative mRNA splicing of CD44 is implicated in CCCa development.
Purpose of the Study:
- To characterize the expression of specific CD44 splice variants (CD44-3v, -5v, -7v, and -10v) in ovarian CCCa.
- To evaluate the prognostic significance of these CD44 variants in ovarian cancer.
- To compare CD44 variant expression between primary tumors and metastatic sites.
Main Methods:
- Immunocytochemistry was employed to analyze CD44-3v, -5v, -7v, and -10v expression.
- Twenty-two cases of ovarian CCCa were studied.
- Expression was compared between primary tumors, metastatic sites, and contralateral nonaffected ovaries.
Main Results:
- Primary ovarian CCCa tumors showed variable expression of CD44-3v (44%), -5v (55%), -7v (61%), and -10v (39%).
- Metastatic sites exhibited significantly decreased CD44 variant immunoreactivity compared to primary tumors.
- Absence of CD44-10v in primary tumors was associated with a lower recurrence and mortality rate (18%) versus its presence (71%, P = 0.049).
Conclusions:
- Aberrant alternative mRNA splicing of CD44 occurs during ovarian CCCa development.
- CD44-10v expression in primary tumors serves as a significant prognostic marker for patient survival.
- Further research with larger cohorts is necessary to elucidate the role of CD44 isoforms in ovarian cancer metastasis.
