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CD44-9v and CD44-10v Are Potential Molecular Markers for Squamous Cell Carcinoma of the Vulva

Inés Sancho-Torres, MD

Darlene G. Gibbon, MD

Luc F. Miller Watelet, PhD

Clara Mesonero, MD

Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Cancer Center, Department of Biostatistics, and Department of Pathology, University of Rochester, Rochester, New York

Objective: CD44 is a cell surface glycoprotein widely distributed in the extracellular matrix. CD44 isoforms arising from alternative mRNA splicing are implicated in tumor metastases. The aim of this study is to investigate the expression of CD44s and two splice variants, CD44-9v and CD44-10v, in squamous cell carcinoma (SCC) of the vulva as well as its correlation with lymph node (LN) metastases and disease-free survival.

Methods: Thirty-five SCC vulvar tumors were evaluated for CD44s, CD44-9v and CD44-10v expression by immunoctyochemistry. One nonmetastatic LN was studied also. In cases with LN metastases, the metastatic LN as well as a nonmetastatic LN from the same patient were evaluated.

Results: CD44s and CD449v were expressed in all epithelia—normal, dysplastic, and SCC. However, intensity and distribution of expression of 9v isoforms changed within the tissue containing invasive cancer. CD44-9v expression was downregulated in the most differentiated cells within the carcinoma, mainly in patients who had disease recurrence or eventually died of disease (P = .031). All metastatic tumor to LNs was immunoreactive also for CD44-9v. CD44-10v expression was present in 78% of tumors and 56% of normal epithelium. Interestingly, CD44-10v membrane expression, but not cytoplasmic expression, correlated with disease recurrence (P = .035).

Conclusion: Our findings warrant larger multi-institutional studies to determine the potential of CD44-9v and CD44-10v as molecular markers of disease recurrence in vulvar carcinoma. We propose to test the use of anti-CD44-9v monoclonal antibody for radioimmunoimaging of a occult LN metastases.

Key Words: CD44 • vulvar carcinoma • metastasis molecular markers

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