title: Decreased expression of hyaluronan synthase 1 and 2 associates with poor prognosis in cutaneous melanoma.
abstract: Hyaluronan is a large extracellular matrix molecule involved in several biological processes such as proliferation, migration and invasion. In many cancers, hyaluronan synthesis is altered, which implicates disease progression and metastatic potential. We have previously shown that synthesis of hyaluronan and expression of its synthases 1-2 (HAS1-2) decrease in cutaneous melanoma, compared to benign melanocytic lesions.
  
  
  
  In the present study, we compared immunohistological staining results of HAS1 and HAS2 with clinical and histopathological parameters to investigate whether HAS1 or HAS2 has prognostic value in cutaneous melanoma. The specimens consisted of 129 tissue samples including superficial (Breslow ≤ 1 mm) and deep (Breslow > 4 mm) melanomas and lymph node metastases. The differences in immunostainings were analysed with non-parametric Mann-Whitney U test. Associations between immunohistological staining results and clinical parameters were determined with the χ(2) test. Survival between patient groups was compared by the Kaplan-Meier method using log rank test and Cox's regression model was used for multivariate analyses.
  
  
  
  The expression of HAS1 and HAS2 was decreased in deep melanomas and metastases compared to superficial melanomas. Decreased immunostaining of HAS2 in melanoma cells was significantly associated with several known unfavourable histopathologic prognostic markers like increased mitotic count, absence of tumor infiltrating lymphocytes and the nodular subtype. Furthermore, reduced HAS1 and HAS2 immunostaining in the melanoma cells was associated with increased recurrence of melanoma (p = 0.041 and p = 0.006, respectively) and shortened disease- specific survival (p = 0.013 and p = 0.001, respectively).
  
  
  
  This study indicates that reduced expression of HAS1 and HAS2 is associated with melanoma progression and suggests that HAS1 and HAS2 have a prognostic significance in cutaneous melanoma.
authors.affiliation: Institute of Biomedicine, University of Eastern Finland, P.O. Box 1627, 70211, Kuopio, Finland.
authors.forename: Mari
authors.initials: M
authors.lastname: Poukka
authors.affiliation: Cancer Center, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Andrey
authors.initials: A
authors.lastname: Bykachev
authors.affiliation: Department of Dermatology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
authors.forename: Hanna
authors.initials: H
authors.lastname: Siiskonen
authors.affiliation: Cancer Center, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Kristiina
authors.initials: K
authors.lastname: Tyynelä-Korhonen
authors.affiliation: Cancer Center, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Päivi
authors.initials: P
authors.lastname: Auvinen
authors.affiliation: Institute of Biomedicine, University of Eastern Finland, P.O. Box 1627, 70211, Kuopio, Finland. sanna.pasonen@uef.fi.
authors.forename: Sanna
authors.initials: S
authors.lastname: Pasonen-Seppänen
authors.affiliation: Institute of Clinical Medicine/Clinical Pathology, University of Eastern Finland, Kuopio, Finland.|Department of Clinical Pathology, Kuopio University Hospital, Kuopio, Finland.|Cancer Center of Eastern Finland, Kuopio, Finland.
authors.forename: Reijo
authors.initials: R
authors.lastname: Sironen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D058851:GPI-Linked Proteins / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000378:metabolism*; D006801:Humans; D000076002:Hyaluronan Synthases; D006821:Hyaluronoglucosaminidase / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D055815:Young Adult
chemical_list: D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins; D014453:Glucuronosyltransferase; C523794:HAS1 protein, human; C101754:HAS2 protein, human; D000076002:Hyaluronan Synthases; C473096:Hyal2 protein, human; D006821:Hyaluronoglucosaminidase
keywords: Hyaluronan; Hyaluronan synthases 1 and 2; Hyaluronidase 2; Lymph node metastasis; Melanoma; Prognosis