title: Hyaluronan synthase and hyaluronidase expression in serous ovarian carcinoma is related to anatomic site and chemotherapy exposure.
abstract: The present study investigated the expression and clinical role of hyaluronan synthases (HAS1-3) and hyaluronidases (Hyal1-3) in serous ovarian carcinoma. HAS and HYAL mRNA expression was analyzed in 97 tumors (61 effusions, 27 primary carcinomas, 9 solid metastases) using PCR and further studied for association with clinicopathologic parameters, including survival. HAS1 mRNA was overexpressed in effusions compared to primary carcinomas and solid metastases (p < 0.001), and an alternatively spliced HAS1 was expressed only in effusions. HAS2 mRNA was overexpressed in solid metastases  and primary carcinomas compared to effusions (p = 0.043), and HAS3 mRNA was overexpressed in primary carcinomas and effusions compared to solid metastases  (p = 0.008). HYAL1 mRNA was absent in all specimens, whereas HYAL2 was expressed  as two splice variants, of which HYAL2-var2 was overexpressed in solid metastases compared to effusions and primary carcinomas (p < 0.001). HYAL3 mRNA was expressed as wild-type and variant 1-3 form, the latter more highly in primary carcinomas and effusions compared to solid metastases (p = 0.006). HAS1 mRNA was overexpressed in  pre- compared to post-chemotherapy effusions (p < 0.001), with opposite finding for HYAL2-var1 and HYAL3-WT (p = 0.016 and p = 0.024, respectively). Higher HYAL2-var1 and HAS1 splice variant mRNA expression in effusions was associated with longer  (p = 0.033) and shorter (p = 0.047) overall survival, respectively. These data are the first to document a role for HAS and Hyal members in tumor progression in ovarian carcinoma, as evidenced by their differential expression as function of anatomic site and chemotherapy exposure, with a possible prognostic role for patients with malignant effusions.
authors.affiliation: Institute of Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel. reich@cc.huji.ac.il.
authors.forename: Ilana
authors.initials: I
authors.lastname: Weiss
authors.forename: Claes G
authors.initials: CG
authors.lastname: Trope
authors.forename: Reuven
authors.initials: R
authors.lastname: Reich
authors.forename: Ben
authors.initials: B
authors.lastname: Davidson
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D002277:Carcinoma / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D005260:Female; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D000076002:Hyaluronan Synthases; D006821:Hyaluronoglucosaminidase / Q000235:genetics / Q000378:metabolism*; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; D020033:Protein Isoforms; D012333:RNA, Messenger; D014453:Glucuronosyltransferase; D000076002:Hyaluronan Synthases; D006821:Hyaluronoglucosaminidase