Loss of basement membrane heparan sulfate expression is associated with pelvic lymph node metastasis in invasive cervical cancer.
Perlecan is a major heparan sulfate proteoglycan of basement membrane (BM) and binds to various cytokines and growth factors via its heparan sulfate glycosaminoglycan (HS-GAG) chains. The aim of this study was to investigate BM HS-GAG expression in invasive cervical cancers. We investigated the expression of BM HS-GAG by immunohistochemistry in 143 invasive cervical cancers and 30 metastatic lymph node samples, and analyzed correlations with various clinicopathological features. Furthermore, the gene expression levels of heparanase were assessed by RT-PCR in 52 invasive cervical cancer samples. HS-GAG expression index was significantly lower in cases of lymph node metastasis (p=0.01). There was no association between HS-GAG expression status and patient outcome. HS-GAG expression index in metastatic pelvic lymph nodes was significantly higher than that in the primary site (p=0.019). Furthermore, HS-GAG expression index was significantly lower in cases where heparanase mRNA expression was detectable (p=0.033). Heparanase mRNA expression is associated with the loss of BM HS-GAG expression, which is closely related to lymph node metastasis in invasive cervical cancers.
Kodama
Junichi
J
Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan. kodama@cc.okayama-u.ac.jp
Shinyo
Yasuhiro
Y
Hasengaowa
Kusumoto
Tomoyuki
T
Seki
Noriko
N
Nakamura
Keiichiro
K
Hongo
Atsushi
A
Hiramatsu
Yuji
Y
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D001485:Basement Membrane / Q000378:metabolism; D018196:Carcinoma, Adenosquamous / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005966:Glucuronidase / Q000235:genetics / Q000378:metabolism; D019812:Heparan Sulfate Proteoglycans / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000099175:Heparanase
D005966:Glucuronidase; D019812:Heparan Sulfate Proteoglycans; D012333:RNA, Messenger; D000099175:Heparanase; C071927:perlecan