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CD44 splice variant expression in clear cell carcinoma of the ovary
L Rodríguez-Rodríguez1, I Sancho-Torres, P Leakey
1Division of Gynecologic Oncology, University of Rochester, Rochester, New York, 14642, USA.
Objective:
CD44 is a surface glycoprotein widely distributed among different tissues. Malignant tumors may show a more complex pattern of CD44 expression, indicating a loss of splice control. The aim of our study is to investigate the expression of CD44 splice variants (CD44v) and its metastatic potential in clear cell carcinoma of the ovary.
Methods:
Twenty-two cases of clear cell carcinoma of the ovary were evaluated for CD44 standard form (CD44s) and splice variants: -4v, -6v, and -9v expression by immunocytochemistry.
Results:
Twenty-one primary ovarian tumors and 23 metastatic sites were available for evaluation. Eighteen of 21 (86%) of ovarian sections studied expressed 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% expressed CD44s. In contrast, only 5 (22%) metastases had CD44-4v and CD44-6v expression and 8 (35%) had CD44-9v immunoreactivity. None of 10 normal contralateral ovaries expressed CD44s or any splice variants. In 2 cases we had tumor available from the primary surgery, and subsequent recurrences. Both 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 normal ovary in the same patient. Metastases of clear cell carcinoma show a downregulation in expression of some splice variants. Furthermore, we have data that suggest that as the tumors recur, CD44s and its isoforms are downregulated. Our results suggest that alternative mRNA splicing of CD44 may be important in the development of metastases from clear cell carcinoma of the ovary.
Insights
Clear cell ovarian carcinoma shows altered CD44 standard form (CD44s) and splice variant expression. Metastases and recurrences exhibit downregulation of CD44 splice variants, suggesting a role in ovarian cancer metastasis.
Area of Science:
- Oncology
- Molecular Biology
- Gynecologic Pathology
Background:
- CD44 is a cell surface glycoprotein involved in cell adhesion and migration.
- Aberrant CD44 splice variant expression is observed in various malignancies.
- Clear cell carcinoma of the ovary (CCOC) is an aggressive subtype with a propensity for metastasis.
Purpose of the Study:
- To investigate the expression patterns of CD44 standard form (CD44s) and specific CD44 splice variants (CD44v) in CCOC.
- To correlate CD44 expression with the metastatic potential of CCOC.
- To examine CD44 expression in recurrent CCOC.
Main Methods:
- Immunocytochemistry was employed to assess CD44s and CD44 splice variants (-4v, -6v, -9v) expression.
- Analysis included 21 primary CCOC tumors and 23 metastatic sites.
- Comparison was made with 10 normal contralateral ovaries.
Main Results:
- CD44s and splice variants were frequently expressed in primary CCOC, unlike normal ovaries.
- Metastatic sites showed reduced expression of CD44-4v, CD44-6v, and CD44-9v compared to primary tumors.
- Recurrent tumors displayed decreased expression of CD44-4v and CD44-6v.
Conclusions:
- CCOC exhibits dysregulated CD44 standard form and splice variant expression compared to normal ovarian tissue.
- Downregulation of certain CD44 splice variants is associated with metastasis and recurrence in CCOC.
- Alternative mRNA splicing of CD44 may play a significant role in the development and progression of CCOC metastasis.