Decreased expression of cd44 in metastatic prostate cancer

Abstract

Decreased expression of CD44 is an independent prognostic marker for surgically treated prostate cancer. To investigate immunohistochemically defined CD44 expression in primary and metastatic prostate cancer, 2 groups of patients undergoing radical prostatectomy for clinically localized prostate cancer were studied. (1) pN1 group: 23 patients, finally staged pN1, of whom the radical prostatectomy specimen and the lymph nodes were investigated to establish a correlation between CD44 expression in the concurrently resected primaries and metastases; (2) pN0 group: 23 patients with pN0 disease matched for pT stage and Gleason sum score with the pN1 patients. Progression rates based on serum prostate‐specific antigen (PSA) levels could be determined in 42 of these 46 patients. In addition, 28 distant metastases were studied. A CD44 score of < 10% was found in 22 of the 23 lymph node metastases (96%) and in 20 of the corresponding radical prostatectomies. In the pN0 group this was observed in only 6 out of 23 specimens. In most of the distant metastases CD44 scores were < 10%. Patients with pN0 disease and > 10% CD44‐positive tumor cells had a significantly better prognosis than the other patients who were not significantly different from each other. CD44 expression is thus strongly reduced in prostate cancer metastases as well as in the corresponding primary tumors. This reduction may be used to predict the N stage clinically, provided that CD44 scores can be determined reliably on preoperative biopsy specimens. Int. J. Cancer (Pred. Oncol.) 84:478–483, 1999. © 1999 Wiley‐Liss, Inc.

Using Molecular Markers to Help Predict Who Will Fail after Radical Prostatectomy

“…Two other studies evaluated CD44. In 97 radical prostatectomy patients [29] with median followup of 84 months, utilizing PSA of >1.0 as failure, most (86%) patients were positive for CD44, so risk was determined by graded intensity of the staining. Decreased expression increased the risk of failure.…”

Co-expression of CD147 (EMMPRIN), CD44v3-10, MDR1 and monocarboxylate transporters is associated with prostate cancer drug resistance and progression

“…The expression of CD44 and its variants is associated with the progression of several cancers, although this remains controversial for CaP (De Marzo et al , 1998; Noordzij et al , 1999). One study reported a complete lack of membranous expression of all CD44 isoforms in 93–98% primary CaP tissues (Kallakury et al , 1996), whereas another reported moderate to high levels of CD44 expression in 60% of primary CaP, with ∼14% of metastases expressing low levels of CD44 (Nagabhusha et al , 1996).…”

Highly purified CD44+ prostate cancer cells from xenograft human tumors are enriched in tumorigenic and metastatic progenitor cells

“…The relationship between CD44 expression and tumor grade is also uncertain -one study shows a strong correlation between Gleason grade of the tumor and loss of CD44 expression (De Marzo et al, 1998), whereas another reports no correlation (Paradis et al, 1998). Furthermore, although CD44 expression is reported to be reduced in metastases (Nagabhushan et al, 1996;De Marzo et al, 1998;Noordzij et al, 1999), the CD44 þ PCa cells are found to predominate in two visceral metastases (Liu et al, 1999). Similar to expression studies, the potential role of CD44 in PCa development and metastases is controversial -although some studies show a tumor-suppressive function of CD44 in overexpression experiments (Gao et al, 1997(Gao et al, , 1998, many other studies implicate CD44 in PCa cell proliferation, adhesion, migration, and invasion in vitro as well as in metastatic dissemination in vivo (Lokeshwar et al, 1995;Paradis et al, 1998;Liu et al, 1999;Draffin et al, 2004;Omara-Opyene et al, 2004).…”