{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T11:45:49Z","timestamp":1773661549765,"version":"3.50.1"},"reference-count":20,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2012,10,10]],"date-time":"2012-10-10T00:00:00Z","timestamp":1349827200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 &lt; 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 &lt; 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 &lt; 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.<\/jats:p>","DOI":"10.3390\/ijms131012925","type":"journal-article","created":{"date-parts":[[2012,10,10]],"date-time":"2012-10-10T20:42:28Z","timestamp":1349901748000},"page":"12925-12938","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Hyaluronan Synthase and Hyaluronidase Expression in Serous Ovarian Carcinoma is Related to Anatomic Site and Chemotherapy Exposure"],"prefix":"10.3390","volume":"13","author":[{"given":"Ilana","family":"Weiss","sequence":"first","affiliation":[{"name":"Institute of Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claes G.","family":"Trope","sequence":"additional","affiliation":[{"name":"Institute of Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel"},{"name":"Department of Gynecologic Oncology, Oslo University Hospital, Norwegian Radium Hospital, Oslo N-310, Norway"},{"name":"Division of Pathology, Oslo University Hospital, Norwegian Radium Hospital, Oslo N-0424, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reuven","family":"Reich","sequence":"additional","affiliation":[{"name":"Institute of Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ben","family":"Davidson","sequence":"additional","affiliation":[{"name":"Division of Pathology, Oslo University Hospital, Norwegian Radium Hospital, Oslo N-0424, Norway"},{"name":"Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo N-0424, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2012,10,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1038\/nrc1123","article-title":"Ovarian cancer: Strategies for overcoming resistance to chemotherapy","volume":"3","author":"Agarwal","year":"2003","journal-title":"Nat. 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