title: Reduced level of CD44 and hyaluronan associated with unfavorable prognosis in clinical stage I cutaneous melanoma.
abstract: The cell surface glycoprotein CD44 and its ligand, hyaluronan (HA), enhance growth and metastatic capacity of melanoma cells in vitro, but their clinical significance in primary cutaneous melanoma is still unclear. Therefore, we studied whether the levels of CD44 and HA associate with disease progression and survival of cutaneous melanoma. A series of 292 clinical stage I cutaneous melanomas was analyzed by immunohistochemistry using an anti-CD44H antibody (clone 2C5). HA was demonstrated histochemically using a biotinylated HA-specific affinity probe (bHABC). The reduced staining levels of CD44 and HA were associated with each other and indicators of progressive disease. Reduced CD44 and HA level, high tumor thickness, high pT category, high Clark's level, bleeding, and male gender predicted short univariate recurrence free survival (RFS) and overall survival (OS). In Cox's multivariate analysis (N: = 251), the decreased level of CD44, high tumor thickness, and bleeding predicted independently short RFS. High tumor thickness and bleeding were associated with short OS. We conclude that the reduced cell surface CD44 and HA levels associate with poor prognosis in clinical stage I cutaneous melanoma. The notion that the decreased level of CD44 independently predicts short RFS suggests that reduced cell surface CD44 enhances the spreading potential in localized cutaneous melanoma and that quantification of CD44 offers a prognostic tool for its clinical evaluation.
authors.affiliation: Department of Surgery, Kuopio University Hospital, Kuopio, Finland.
authors.forename: J M
authors.initials: JM
authors.lastname: Karjalainen
authors.forename: R H
authors.initials: RH
authors.lastname: Tammi
authors.forename: M I
authors.initials: MI
authors.lastname: Tammi
authors.forename: M J
authors.initials: MJ
authors.lastname: Eskelinen
authors.forename: U M
authors.initials: UM
authors.lastname: Agren
authors.forename: J J
authors.initials: JJ
authors.lastname: Parkkinen
authors.forename: E M
authors.initials: EM
authors.lastname: Alhava
authors.forename: V M
authors.initials: VM
authors.lastname: Kosma
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D008297:Male; D008545:Melanoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis; D015996:Survival Rate
chemical_list: D018960:Hyaluronan Receptors; D006820:Hyaluronic Acid