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.
| Original language | English |
|---|---|
| Pages (from-to) | 354-361 |
| Number of pages | 8 |
| Journal | Annals of Diagnostic Pathology |
| Volume | 16 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - Oct 2012 |
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Keywords
- Carcinoma in situ
- Cyclooxygenase-2
- Heparanase
- Oral carcinogenesis
- Oral epithelial dysplasia
- Oral squamous cell carcinoma
ASJC Scopus subject areas
- Pathology and Forensic Medicine
Cite this
Heparanase and cyclooxygenase-2 gene and protein expressions during progression of oral epithelial dysplasia to carcinoma. / Nagatsuka, Hitoshi; Siar, Chong Huat; Tsujigiwa, Hidetsugu; Naomoto, Yoshio; Han, Phuu Pwint; Gunduz, Mehmet; Sugahara, Toshio; Sasaki, Akira; Nakajima, Motowo.
In: Annals of Diagnostic Pathology, Vol. 16, No. 5, 10.2012, p. 354-361.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Heparanase and cyclooxygenase-2 gene and protein expressions during progression of oral epithelial dysplasia to carcinoma
AU - Nagatsuka, Hitoshi
AU - Siar, Chong Huat
AU - Tsujigiwa, Hidetsugu
AU - Naomoto, Yoshio
AU - Han, Phuu Pwint
AU - Gunduz, Mehmet
AU - Sugahara, Toshio
AU - Sasaki, Akira
AU - Nakajima, Motowo
PY - 2012/10
Y1 - 2012/10
N2 - 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.
AB - 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.
KW - Carcinoma in situ
KW - Cyclooxygenase-2
KW - Heparanase
KW - Oral carcinogenesis
KW - Oral epithelial dysplasia
KW - Oral squamous cell carcinoma
UR - http://www.scopus.com/inward/record.url?scp=84866120367&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84866120367&partnerID=8YFLogxK
U2 - 10.1016/j.anndiagpath.2012.02.004
DO - 10.1016/j.anndiagpath.2012.02.004
M3 - Article
C2 - 22575501
AN - SCOPUS:84866120367
VL - 16
SP - 354
EP - 361
JO - Annals of Diagnostic Pathology
JF - Annals of Diagnostic Pathology
SN - 1092-9134
IS - 5
ER -