Immunohistochemical and serological evaluation of CD44 splice variants in human ovarian cancer

Abstract

Summary The surface glycoprotein CD44 is widely distributed in different tissues. In contrast to healthy tissue, tumour samples show a more complex pattern of CD44 expression, indicating a loss of splice control. Beside cell-surface expression, the measurement of soluble CD44 in serum of cancer patients could be useful in early diagnosis and assessment of disease status. We evaluated the surface expression of CD44 isoforms in 22 ovarian cancer patients by means of immunohistochemistry. Additionally, we investigated 134 serological samples of these patients for the occurrence of CD44 isoform expression. For CD44standard, CD44v5 and CF44v6 mean serum levels in patients with clinically detectable or non-detectable ovarian cancer were 422.4 ± 143.8 ng ml-and 547.4 ± 148.2 ng ml ', 12.3 ± 7.9 ng ml-' and 21.9 ± 12.2 ng ml-' and 105.5 + 37.9 ng ml-' and 144.9 ± 50.9 ng ml-' respectively (P-values not significant). CD44 surface proteins containing epitopes encoded by splice variants CD44v5, CD44v6 and CD44v7-8 were immunohistochemically detected in 9% (n = 2), 13% (n = 3) and 4% (n = 1) of the 22 tumour samples respectively. In the present study we showed that in ovarian cancer CD44 isoforms CD44v5 and CD44v6 are expressed in very low amounts by the tumours. In accordance with this, we found that the presence of tumour is not associated with higher serum levels of CD44standard, CD44v5 and CD44v6 in preoperative serum samples in ovarian cancer patients. Keywords CD44; alternative splicing, ovarian neoplasms; serum; immunohistochemistry Ovarian cancer is diagnosed at advanced stages in approximately 75% of patients. The prognosis in ovarian cancer remains poor, and there is a need to identify patients less likely to respond to treatment or patients who suffer from low-stage disease and have a worse prognosis. Early detection of ovarian cancer or of recurrent disease after primary therapy is very important in ovarian cancer patients. Serum tumour markers, which have been shown to be useful in early detection of primary tumours, recurrences, evaluation of prognosis and monitoring of therapy, have become an integral part of follow-up schemes in the management of ovarian cancer patients (Tarin and Matsumura, 1993; Dall et al., 1994;Gold and Osband, 1994).The surface glycoprotein CD44 is widely distributed in different tissues (Flanagan et al., 1989). CD44 cell-surface adhesion molecules have been shown to mediate cell-cell and cell-matrix interactions (Screaton et al., 1992), allowing circulating lymphocytes to migrate into lymphatic tissue (Jalkanen et al., 1986;Salles et al., 1993) and to control lymphocyte binding to peripheral lymph nodes, mucosal and synovial endothelial cells (Jalkanen et al., 1987a (Salles et al., 1993).Antibodies raised against different soluble CD44 molecules allow the detection of CD44 isoforms in serum samples. The measurement of soluble CD44 molecules in body fluids could be useful in early diagnosis of cancer, assessment of disease status and evaluation of metastatic potential and prognosis.In ...

Preoperative serum CD26 levels: diagnostic efficiency and predictive value for colorectal cancer

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The prognostic value of CD44 isoform expression in endometrial cancer

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