| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Regular Articles |
From the Institute of Pathology*
and theDepartment of Gynecology and Obstetrics,
Charité Hospital, Berlin; the EpidemiologyUnit,
Institute of Public Health, TechnicalUniversity of Berlin, Berlin; and the Institute ofPathology,
Rheinisch WestfälischeTechnische Hochschule, Aachen, Germany
Cyclooxygenase-2 (COX-2) is the rate-limiting enzyme in prostanoid biosynthesis and is involved in tumor progression. We investigated expression of COX-1 and COX-2 in cell lines and tumors from ovarian carcinomas. Expression of COX-2 mRNA and protein was detectable in three of five ovarian carcinoma cell lines and was inducible by interleukin-1ß or phorbolester in a subset of cell lines. Prostaglandin E2 (PGE2) production could be inhibited by the selective COX-2 inhibitor NS-398. In malignant ascites of ovarian carcinomas significantly increased levels of PGE2 were found compared to other carcinomas or nonmalignant ascites (P = 0.03). We investigated expression of COX-2 by immunohistochemistry in 117 ovarian surface epithelial tumors. Expression of COX-2 was detected in 42% of 86 ovarian carcinomas and in 37% of 19 low malignant potential tumors, but not in 12 cystadenomas or 2 normal ovaries. Expression of COX-1 was detected by immunohistochemistry in 75% of 75 invasive ovarian carcinomas and in 75% of 16 low malignant potential tumors, whereas 2 samples from normal ovaries and 8 cystadenomas were positive for COX-1. In univariate survival analysis of invasive carcinomas, expression of COX-2 was associated with a significantly reduced median survival time (log rank test, P = 0.04). For patients younger than 60 years of age, this association was even more significant (P < 0.004). In contrast, expression of COX-1 was no prognostic parameter (P = 0.89). There was no significant correlation between COX-2 or COX-1 expression and other clinicopathological markers. In multivariate analysis expression of COX-2 was an independent prognostic factor for poor survival (relative risk, 2.74; 95% CI, 1.38 to 5.47). Our data indicate that COX-2 expression is an independent prognostic factor in ovarian carcinoma. Based on the results of this study, it would be interesting to investigate whether ovarian carcinoma patients with tumors positive for COX-2 would benefit from treatment with selective COX-2 inhibitors.
This article has been cited by other articles:
 |
|
 |
|
  S. Donnini, F. Finetti, R. Solito, E. Terzuoli, A. Sacchetti, L. Morbidelli, P. Patrignani, and M. Ziche EP2 prostanoid receptor promotes squamous cell carcinoma growth through epidermal growth factor receptor transactivation and iNOS and ERK1/2 pathways FASEB J, August 1, 2007; 21(10): 2418 - 2430. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Stadlmann, U. Gueth, E. Wight, L. A Kunz-Schughart, A. Hartmann, and G. Singer Expression of peroxisome proliferator activated receptor {gamma} and cyclo-oxygenase 2 in primary and recurrent ovarian carcinoma J. Clin. Pathol., March 1, 2007; 60(3): 307 - 310. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Y. Ting, B. F. Kimler, C. J. Fabian, and B. K. Petroff Characterization of a preclinical model of simultaneous breast and ovarian cancer progression Carcinogenesis, January 1, 2007; 28(1): 130 - 135. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Tsubochi, N. Sato, M. Hiyama, M. Kaimori, S. Endo, Y. Sohara, and T. Imai Combined Analysis of Cyclooxygenase-2 Expression With p53 and Ki-67 in Nonsmall Cell Lung Cancer. Ann. Thorac. Surg., October 1, 2006; 82(4): 1198 - 1204. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Siironen, A. Ristimaki, K. Narko, S. Nordling, J. Louhimo, S. Andersson, R. Haapiainen, and C. Haglund VEGF-C and COX-2 expression in papillary thyroid cancer. Endocr. Relat. Cancer, June 1, 2006; 13(2): 465 - 473. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. K. Yiu and A. Toker NFAT Induces Breast Cancer Cell Invasion by Promoting the Induction of Cyclooxygenase-2 J. Biol. Chem., May 5, 2006; 281(18): 12210 - 12217. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Lee, J. Frischer, A. Serur, J. Huang, J.-O Bae, Z. N. Kornfield, L. Eljuga, C. J. Shawber, N. Feirt, M. Mansukhani, et al. Inhibition of cyclooxygenase-2 disrupts tumor vascular mural cell recruitment and survival signaling. Cancer Res., April 15, 2006; 66(8): 4378 - 4384. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Bagnato, F. Spinella, and L. Rosano Emerging role of the endothelin axis in ovarian tumor progression Endocr. Relat. Cancer, December 1, 2005; 12(4): 761 - 772. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Shoji, M. Takahashi, N. Takasuka, N. Niho, T. Kitamura, H. Sato, T. Maruyama, Y. Sugimoto, S. Narumiya, T. Sugimura, et al. Prostaglandin E receptor EP3 deficiency modifies tumor outcome in mouse two-stage skin carcinogenesis Carcinogenesis, December 1, 2005; 26(12): 2116 - 2122. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Vallbohmer, W. Zhang, M. Gordon, D. Y. Yang, J. Yun, O. A. Press, K. E. Rhodes, A. E. Sherrod, S. Iqbal, K. D. Danenberg, et al. Molecular Determinants of Cetuximab Efficacy J. Clin. Oncol., May 20, 2005; 23(15): 3536 - 3544. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Daikoku, D. Wang, S. Tranguch, J. D. Morrow, S. Orsulic, R. N. DuBois, and S. K. Dey Cyclooxygenase-1 Is a Potential Target for Prevention and Treatment of Ovarian Epithelial Cancer Cancer Res., May 1, 2005; 65(9): 3735 - 3744. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Heinonen, P. Bono, K. Narko, S.-H. Chang, J. Lundin, H. Joensuu, H. Furneaux, T. Hla, C. Haglund, and A. Ristimaki Cytoplasmic HuR Expression Is a Prognostic Factor in Invasive Ductal Breast Carcinoma Cancer Res., March 15, 2005; 65(6): 2157 - 2161. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Symowicz, B. P. Adley, M. M.M. Woo, N. Auersperg, L. G. Hudson, and M. S. Stack Cyclooxygenase-2 Functions as a Downstream Mediator of Lysophosphatidic Acid to Promote Aggressive Behavior in Ovarian Carcinoma Cells Cancer Res., March 15, 2005; 65(6): 2234 - 2242. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Spinella, L. Rosano, V. Di Castro, P. G. Natali, and A. Bagnato Endothelin-1-induced Prostaglandin E2-EP2, EP4 Signaling Regulates Vascular Endothelial Growth Factor Production and Ovarian Carcinoma Cell Invasion J. Biol. Chem., November 5, 2004; 279(45): 46700 - 46705. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Sirois, K. Sayasith, K. A. Brown, A. E. Stock, N. Bouchard, and M. Dore Cyclooxygenase-2 and its role in ovulation: a 2004 account Hum. Reprod. Update, September 1, 2004; 10(5): 373 - 385. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Spinella, L. Rosano, V. Di Castro, M. R. Nicotra, P. G. Natali, and A. Bagnato Inhibition of Cyclooxygenase-1 and -2 Expression by Targeting the Endothelin A Receptor in Human Ovarian Carcinoma Cells Clin. Cancer Res., July 15, 2004; 10(14): 4670 - 4679. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T.-L. Erkinheimo, H. Lassus, P. Finne, B. P. van Rees, A. Leminen, O. Ylikorkala, C. Haglund, R. Butzow, and A. Ristimaki Elevated Cyclooxygenase-2 Expression Is Associated with Altered Expression of p53 and SMAD4, Amplification of HER-2/neu, and Poor Outcome in Serous Ovarian Carcinoma Clin. Cancer Res., January 15, 2004; 10(2): 538 - 545. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Denkert, W. Weichert, S. Pest, I. Koch, D. Licht, M. Kobel, A. Reles, J. Sehouli, M. Dietel, and S. Hauptmann Overexpression of the Embryonic-Lethal Abnormal Vision-like Protein HuR in Ovarian Carcinoma Is a Prognostic Factor and Is Associated with Increased Cyclooxygenase 2 Expression Cancer Res., January 1, 2004; 64(1): 189 - 195. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. B. Perchick and H. N. Jabbour Cyclooxygenase-2 Overexpression Inhibits Cathepsin D-Mediated Cleavage of Plasminogen to the Potent Antiangiogenic Factor Angiostatin Endocrinology, December 1, 2003; 144(12): 5322 - 5328. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T.-L. Erkinheimo, H. Lassus, A. Sivula, S. Sengupta, H. Furneaux, T. Hla, C. Haglund, R. Butzow, and A. Ristimaki Cytoplasmic HuR Expression Correlates with Poor Outcome and with Cyclooxygenase 2 Expression in Serous Ovarian Carcinoma Cancer Res., November 15, 2003; 63(22): 7591 - 7594. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Choy and L. Milas Enhancing Radiotherapy With Cyclooxygenase-2 Enzyme Inhibitors: A Rational Advance? J Natl Cancer Inst, October 1, 2003; 95(19): 1440 - 1452. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Mandelin, H. Lassus, M. Seppala, A. Leminen, J.-A. Gustafsson, G. Cheng, R. Butzow, and R. Koistinen Glycodelin in Ovarian Serous Carcinoma: Association with Differentiation and Survival Cancer Res., October 1, 2003; 63(19): 6258 - 6264. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Agarwal, C. Denkert, and S. Hauptmann The Function of COX-2 in Human Ovarian Carcinoma Am. J. Pathol., July 1, 2003; 163(1): 368 - 369. [Full Text] [PDF]
|
|
|
|
 |
|
 T. P. Connolly Cyclooxygenase-2 Inhibitors in Gynecologic Practice Clin. Med. Res., April 1, 2003; 1(2): 105 - 110. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. L. Konger, G. A. Scott, Y. Landt, J. H. Ladenson, and A. P. Pentland Loss of the EP2 Prostaglandin E2 Receptor in Immortalized Human Keratinocytes Results in Increased Invasiveness and Decreased Paxillin Expression Am. J. Pathol., December 1, 2002; 161(6): 2065 - 2078. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
