title: Coexpression of COX-2 and iNOS in Angiogenesis of Superficial Esophageal Squamous Cell Carcinoma.
abstract: Using immunohistochemical staining, the present study was conducted to examine whether cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) affect angiogenesis in early-stage esophageal squamous cell carcinoma (ESCC). We also analyzed the correlation between these two factors. Cyclooxygenase 2, iNOS, and angiogenesis in early-stage ESCC are unclear. Using 10 samples of normal squamous epithelium, 7 samples of low-grade intraepithelial neoplasia (LGIN), and 45 samples of superficial esophageal cancer, we observed the expression of COX-2 and iNOS. We then investigated the COX-2 and iNOS immunoreactivity scores and the correlation between COX-2 or iNOS scores and microvessel density (MVD) using CD34 or CD105. The intensity of COX-2 or iNOS expression differed significantly according to histological type (P < 0.001). The scores of COX-2 and iNOS were lowest for normal squamous epithelium, followed in ascending order by LGIN, carcinoma in situ and tumor invading the lamina propria mucosae (M1-M2 cancer); and tumor invading the muscularis mucosa (M3) or deeper cancer. The differences were significant (P < 0.001). Cancers classified M1-M2 (P < 0.01 and P < 0.05, respectively); M3; or deeper cancer (P < 0.01) had significantly higher COX-2 and iNOS scores than normal squamous epithelium. There was a significant correlation between COX-2 and iNOS scores (P < 0.001, rs = 0.51). Correlations between COX-2 score and CD34-positive MVD or CD105-positive MVD were significant (rs = 0.53, P < 0.001; rs = 0.62, P < 0.001, respectively). Inducible nitric oxide synthase score was also significantly correlated with CD34 MVD and CD105 MVD (rs = 0.45, P < 0.001; rs = 0.60, P < 0.001, respectively). Chemoprevention of COX-2 or iNOS activity may blunt the development of ESCC from precancerous lesions.
authors: 1 Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, Saitama, Japan.
authors: Youichi
authors: Y
authors: Kumagai
authors: Jun
authors: J
authors: Sobajima
authors: Morihiro
authors: M
authors: Higashi
authors: Toru
authors: T
authors: Ishiguro
authors: Minoru
authors: M
authors: Fukuchi
authors: Keiichiro
authors: K
authors: Ishibashi
authors: Erito
authors: E
authors: Mochiki
authors: Koji
authors: K
authors: Yakabi
authors: Tatsuyuki
authors: T
authors: Kawano
authors: Jun-ichi
authors: J
authors: Tamaru
authors: Hideyuki
authors: H
authors: Ishida
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000201:enzymology* / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D006801:Humans; D007150:Immunohistochemistry; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000201:enzymology*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2
keywords: Angiogenesis; CD105; CD34; COX-2; Esophageal cancer; iNOS