Role of cyclooxygenase‐2 in immunomodulation and prognosis of endometrial carcinoma

• Published in: International journal of cancer Vol. 114; no. 5; pp. 696 - 701
• Main Authors: Ohno, Yumiko, Ohno, Satoshi, Suzuki, Nobutaka, Kamei, Tsutomu, Inagawa, Hiroyuki, Soma, Gen‐Ichiro, Inoue, Masaki
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.05.2005; Wiley-Liss
• Subjects: Adult; Aged; Apoptosis; Biological and medical sciences; Carcinoma - enzymology; CD8+ T cell; CD8-Positive T-Lymphocytes - enzymology; COX‐2; Cyclooxygenase 2; endometrial cancer; Endometrial Neoplasms - enzymology; Female; Female genital diseases; Gynecology. Andrology. Obstetrics; Humans; Immunohistochemistry; immunomodulation; Lymphatic Metastasis; Medical sciences; Membrane Proteins; Middle Aged; Myometrium - metabolism; Neovascularization, Pathologic; Prognosis; Proportional Hazards Models; Prostaglandin-Endoperoxide Synthases - biosynthesis; Recurrence; Time Factors; Tumors; Human; Endometrium cancer; Prognosis; Immune response; COX-2; Enzyme; Immunomodulation; Cyclooxygenase 2; Malignant tumor; Cell subpopulation; Endometrial carcinoma; CD8+ T cell; Female genital diseases; Cancerology; T-Lymphocyte; Uterine diseases; endometrial cancer; Suppressive cell; Oxidoreductases
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.20777

Although there are several hypotheses explaining the mechanisms of immune‐privileged status of malignant tumor, the exact pathway has yet to be explored. Cyclooxygenase (COX)‐2 plays a vital role in prognosis of cancer patients in terms of contribution to neoangiogenesis and apoptosis inhibition; however, the impact of COX‐2 in immunomodulation has not been reported. We have evaluated the expression of COX‐2 and its impact on infiltration of immune‐competent cells into the tumor cell nest in endometrial carcinoma. Tissue specimens from 70 endometrial carcinoma patients who had undergone a curative resection were evaluated for COX‐2 expression and host immune status (CD8+ T cells). COX‐2 expression was associated with FIGO stage and myometrial invasion, but there was no statistically significant impact. CD8+ T cells within cancer cell nest (Nest CD8) were inversely correlated with the expression level of COX‐2 (p = 0.0006). Nest CD8 became an independent predictor of patient survival (Hazard ratio = 10.300, p = 0.0304) in Cox's multivariate analysis. The expression level of COX‐2 was found to be a significant predictor of disease relapse in univariate analysis (p = 0.0294) but not in multivariate analysis (p = 0.5949). In conclusion, increased nest CD8 produced a survival advantage in endometrial carcinoma patients. Moreover, tumor‐produced COX‐2, which reduces the infiltration of CD8+ T cells into cancer cell nests, may allow tumors to avoid immune surveillance. © 2004 Wiley‐Liss, Inc.