Role of cyclooxygenase-2 and inducible nitric oxide synthase in pancreatic cancer.
OBJECTIVE
Recently, it has been recognized that both cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) produce important endogenous factors of human tumor progression. However, the clinicopathological and biological significance of the expression of COX-2 and iNOS in pancreatic cancer remains unclear. The objective of this study is to find the possible roles and clinical significance of COX-2 and iNOS expression in pancreatic cancer.


METHODS
Seventy-two pancreatic adenocarcinoma tissue specimens were obtained through surgical resection. We investigated the immunohistochemical expression of COX-2 and iNOS in respect to variable clinicopathological characteristics, proliferation activity (by Ki-67 expression), apoptosis (by terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling stain), and microvessel density (by CD34 expression; angiogenesis).


RESULTS
Immunohistochemical investigations demonstrated immunolabeling of tumor cells with the primary antibodies, bovine anti-iNOS and anti-COX-2 antibodies. The COX-2 and iNOS positive rates were 41.7 and 66.7%, respectively. There was significant correlation between positive COX-2 and positive iNOS expression (P = 0.043). The proliferation index (Ki-67 labeling index) was higher in COX-2 positive specimens compared to COX-2 negative specimen (P = 0.015). The apoptotic index of positive iNOS expressions was significantly higher than negative expressions (P < 0.001). The expression of COX-2 and iNOS proteins did not correlate with age, sex, serum bilirubin, CA-19-9, location, size, American Joint Committee on Cancer stage, differentiation, distant metastasis, patient survival, or microvessel density.


CONCLUSIONS
Although the pattern of positive expression was similar in both enzymes, the effect on tumor progression differed; iNOS expression may play a role in apoptosis of tumor cell, while COX-2 expression may contribute to tumor proliferation. However, COX-2 and iNOS expression is not related to prognosis in patients with pancreatic cancer.
Kong
Gu
G
Department of Pathology, Hanyang University School of Medicine, Seoul, Korea.
Kim
Eun Kyung
EK
Kim
Wan Sup
WS
Lee
Kyu Taek
KT
Lee
Yong Wook
YW
Lee
Jong Kyun
JK
Paik
Seung Woon
SW
Rhee
Jong Chul
JC
D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology* / Q000503:physiopathology*; D000368:Aged; D051546:Cyclooxygenase 2; D005260:Female; D006801:Humans; D020287:In Situ Nick-End Labeling; D007527:Isoenzymes / Q000032:analysis* / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009367:Neoplasm Staging; D019001:Nitric Oxide Synthase / Q000032:analysis* / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II; D010190:Pancreatic Neoplasms / Q000401:mortality / Q000473:pathology* / Q000503:physiopathology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis* / Q000502:physiology*; D015996:Survival Rate
D007527:Isoenzymes; D008565:Membrane Proteins; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases