Cyclooxygenase-2 expression in squamous dysplasia and squamous cell carcinoma of the esophagus.
Cyclooxygenase-2 (cox-2) overexpression has been observed in several types of human cancers and has been implicated in carcinogenesis. To elucidate the role of cox-2 in esophageal carcinogenesis, we evaluated the expression of cox-2 in normal squamous epithelium squamous epithelial dysplasia (n=47), and squamous cell carcinoma of the esophagus (n=86) by immunohistochemistry, reverse transcription-PCR assay, and western blotting. A significant overexpression of cox-2 was observed in esophageal squamous dysplasia and squamous cell carcinoma compared with normal squamous epithelium. The immunoreactive score of cox-2 expression, an index determined by intensity and positivity of cox-2 staining, was 0.71 +/- 0.46 (mean +/- SD) in normal squamous esophagus, 2.19 +/- 1.79 in squamous epithelial dysplasia, and 2.67 +/- 1.77 in squamous cell carcinoma. The results of immunohistochemistry were confirmed by a reverse transcription-PCR assay and western blotting analysis. Cox-2 expression level was correlated with proliferation activity assessed by proliferating cell nuclear antigen (PCNA) index and MIB-1 index in dysplastic lesion (r=0.55, P<0.01 with PCNA and r=0.72, P<0.01 with MIB-1) and carcinoma (r=0.56, P<0.01 with PCNA and r=0.72, P<0.01 with MIB-1). Elevated cox-2 expression was associated with high p53 expression (p<0.001) but not with clinicopathological features including age, sex, tumor size, histological grade, lymph node metastasis, and TNM stage. The results indicated that cox-2 may be involved in an early stage of squamous carcinogenesis of the esophagus, and that cox-2 overexpression was related to cell proliferation in esophageal squamous dysplasia and squamous cell carcinoma.
Yu
Hong-Ping
HP
Institute of Environmental Medicine, Tongji Medical College of Muazhong University of Science and Technology, Wuhan 430030, China.
Xu
Shun-Qing
SQ
Liu
Li
L
Shi
Lu-Yuan
LY
Cai
Xiao-Kun
XK
Lu
Wen-Hong
WH
Lu
Bin
B
Su
Yan-Hua
YH
Li
Yuan-Yuan
YY
D000704:Analysis of Variance; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D002455:Cell Division; D051546:Cyclooxygenase 2; D004938:Esophageal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D004947:Esophagus / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000235:genetics*; D019394:Ki-67 Antigen / Q000032:analysis; D008565:Membrane Proteins; D009367:Neoplasm Staging; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
D007527:Isoenzymes; D019394:Ki-67 Antigen; D008565:Membrane Proteins; D012333:RNA, Messenger; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases