Loss of cell-surface heparan sulfate expression in both cervical intraepithelial neoplasm and invasive cervical cancer.
OBJECTIVE
Syndecan-1 binds to various extracellular matrix components via its heparan sulfate glycosaminoglycans (HS-GAG) and most of its biological functions are considered to be associated with this process. The aims of this study are to investigate its expression in cervical neoplasms.


METHODS
We investigated the expression of both the syndecan-1 core protein and cell-surface HS-GAG by immunohistochemistry in 53 cervical intraepithelial neoplasm (CIN), 19 microinvasive, 143 invasive cervical cancers, and 29 metastatic lymph node samples, and analyzed correlations with various clinicopathological features.


RESULTS
The progression of CIN to early invasive cancer was found to associate with reduced levels of both syndecan-1 and HS-GAG expression. In squamous cell carcinomas, HS-GAG expression was significantly lower in cases with lymph-vascular space invasion. Additionally, the overall survival rates for patients exhibiting low HS-GAG expression was significantly lower than patients exhibiting high HS-GAG expression (P = 0.019). Low HS-GAG expression in positive nodes was determined to be a disease-free and overall survival prognostic factor (P = 0.028 and P = 0.018, respectively).


CONCLUSIONS
The loss of syndecan-1 and HS-GAG expression is an early event in cervical carcinogenesis. The loss of HS-GAG expression particularly in positive nodes can serve as an indicator of aggressive disease potential and poor prognosis in patients with invasive cervical cancer.
Shinyo
Yasuhiro
Y
Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan.
Kodama
Junichi
J
Hasengaowa
Kusumoto
Tomoyuki
T
Hiramatsu
Yuji
Y
D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D005260:Female; D006497:Heparan Sulfate / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D008207:Lymphatic Metastasis; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D011509:Proteoglycans / Q000096:biosynthesis; D053668:Syndecan-1; D053667:Syndecans; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D002578:Uterine Cervical Dysplasia / Q000378:metabolism* / Q000473:pathology / Q000601:surgery
D006497:Heparan Sulfate; D008562:Membrane Glycoproteins; D011509:Proteoglycans; D053668:Syndecan-1; D053667:Syndecans; C508241:SDC1 protein, human