Heparanase and cyclooxygenase-2 gene and protein expressions during progression of oral epithelial dysplasia to carcinoma.

Abstract

Heparanase and cyclooxygenase-2 (COX-2) are 2 key enzymes that modulate diverse physiological processes during embryonic development and in adult life. Their deregulations have been implicated in the growth and progression of many cancer types. To date, comparatively little is known about the roles of these molecules during oral carcinogenesis. The aim of this study was to investigate the expression patterns of heparanase and COX-2 during progression of oral epithelial dysplasia (OED) to carcinoma. In situ hybridization and immunohistochemistry were performed on 5 cases of normal mucosa, 15 cases of OED, 5 cases of carcinoma in situ and/or microinvasive carcinoma, and 40 cases of oral squamous cell carcinoma (OSCC). Results demonstrated that heparanase and COX-2 messenger RNA and protein were absent in normal oral mucosa but were coexpressed in increasing intensity as OED progressed to OSCC. Concomitant heparanase- and COX-2-positive staining in the stromal cells suggests that OED/OSCC progression may be modulated by stromal-cancer cell interactions. Diffuse intense staining of poorly differentiated OSCC compared with staining localized to tumor nest periphery in well- and moderately differentiated OSCC suggests that heparanase and COX-2 overexpressions correlated with tumor grade. Strong expression of these enzymes in tumor cells at the advancing front suggests a role in local tumor spread. These results, taken together, suggest that heparanase and COX-2 might play complementary roles in the stepwise progression of OED to carcinoma.

• Authors: Hitoshi Nagatsuka, Chong Huat Siar, Hidetsugu Tsujigiwa, Yoshio Naomoto, Phuu Pwint Han, Mehmet Gunduz, Toshio Sugahara, Akira Sasaki, Motowo Nakajima
• Journal: Annals of diagnostic pathology (Ann Diagn Pathol) Vol. 16 Issue 5 Pg. 354-61 (Oct 2012) ISSN: 1532-8198 [Electronic] United States
• PMID: 22575501 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers, Tumor
• RNA, Messenger
• Cyclooxygenase 2
• heparanase
• Glucuronidase

Topics

• Biomarkers, Tumor (metabolism)
• Carcinoma in Situ (enzymology, genetics, pathology)
• Carcinoma, Squamous Cell (diagnosis, enzymology, genetics)
• Cyclooxygenase 2 (genetics, metabolism)
• Disease Progression
• Epithelial Cells (enzymology, pathology)
• Gene Expression Regulation, Enzymologic (physiology)
• Glucuronidase (genetics, metabolism)
• Humans
• Immunohistochemistry
• In Situ Hybridization
• Mouth Mucosa (pathology)
• Mouth Neoplasms (diagnosis, enzymology, genetics)
• Neoplasm Invasiveness
• RNA, Messenger (metabolism)