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Original Research

Open Access

Expression of cyclooxygenase-2 in endometrial adenocarcinoma

  • G. Kilic1,*,
  • B. Gurates2
  • J. Garon3
  • H. Kang1
  • B. Arun4
  • C.E. Lampley1
  • R. Kurzel1
  • R. Ashfaq5

1Department of Obstetrics and Gynecology, Chicago Medical School, Finch University of the Health Sciences, Mount Sinai Hospital, Chicago, USA

2Department of Obstetrics and Gynecology, University of Illinois, Chicago, USA

3Department of Pathology, Chicago Medical School- Finch University of the Health Sciences, Mount Sinai Hospital, Chicago (IL), USA

4Medical Oncology, MD Anderson Cancer Center, Houston, USA

DOI: 10.12892/ejgo200503271 Vol.26,Issue 3,May 2005 pp.271-274

Published: 10 May 2005

*Corresponding Author(s): G. Kilic E-mail:

Abstract

Studies have shown that COX-2 is up-regulated in several epithelial carcinomas. In this study, we wish to elucidate if endometrial cyclooxygenase-2 (COX-2) expression in endometrial adenocarcinoma is increased relative to normal endometrium. Thirty-six deparaffinized tissue sections from patients with endometrial adenocarcinoma were analyzed by immunohistochemistry for the presence of COX-2. A control group consisted of 13 age-matched patients without malignancy, who underwent surgery for uterine prolapse. Statistical analysis was performed using the Kruskal-Wallis test; differences between groups were evaluated using the Fisher's Exact Test. We found that COX-2 expression was markedly increased in 13 of 36 patients (36.1%) with endometrial adenocarcinoma: in contrast only one of 13 (7.7%) control patients demonstrated increased COX-2 expression (p < or = 0.05). Eight of the 13 COX-2 positive patients in the study had well differentiated adenocarcinoma; the remaining five COX-2 positive patients had moderately and poorly differentiated adenocarcinoma (4 and 1, respectively). In conclusion, COX-2 expression in the endometrium is associated with endometrial adenocarcinoma, especially of the well differentiated type. This may provide an avenue for chemoprevention of endometrial adenocarcinoma. In addition, with new selective inhibitory drugs being developed, inhibition of COX-2 may play an adjunctive role approach to standard therapy, especially for well-differentiated endometrial carcinoma. Further studies are required to investigate the role of COX-2 expression in carcinogenesis.

Keywords

COX-2; Endometrial cancer; Immunohistochemistry; Aromatase

Cite and Share

G. Kilic,B. Gurates,J. Garon,H. Kang,B. Arun,C.E. Lampley,R. Kurzel,R. Ashfaq. Expression of cyclooxygenase-2 in endometrial adenocarcinoma. European Journal of Gynaecological Oncology. 2005. 26(3);271-274.

References

[1] Cancer Facts and Figures 2001, American Cancer Society Inc. 5.

[2] Kurman R.J., Zaino R.J., Norris H.J.: "Endometrial carcinoma" In: Kurman R.J. (eds.). Blaustein's Pathology of the Female Genital Tract. 4''ed. New York: Springer-Verlag, 1994, 443.

[3] Smith W.: "Prostanoid biosynthesis and mechanism of action" (abstract). Am. J. Physiol., 1992, 263, F181.

[4] Kujubu D.A., Fletcher B.S., Varnum B.C., Lim R.W., Herschman H.R.: "A phorbol ester tumor promoter-inducible mRNA from Swiss 3T3 cells". J. Biol. Chem., 1991, 266, 12866.

[5] Sheehan K.M., Sheehan K., O'Donoghue D.P., MacSweeney F., Conroy R.M., Fitzgerald D.J., Murray F.E.: "The relationship between COX-2 expression and colorectal cancer". JAMA, 1999, 282, 1254.

[6] Giardiello F.M., Hamilton S.R.. Krush A.J., Piantadosi S., Hylind L.M., Celano P. et al.: "Treatment of colonic and rectal adenomas with sulindac in familial adenomatous polyposis". N. Engl. J. Med., 1993, 328, 1313.

[7] Thun M.J., Namboodiri M.M., Heath C.W. Jr.: "Aspirin use and reduced risk of fatal colon cancer". N. Engl. J. Med., 1991, 325, 1593.

[8] Holmang S., Cano M., Grenabo L.. Hedelin H., Jhonsson S.L. "Effect of indomethacin on N-4-5-nitro 2- furyl-2 thiazolyl formamide induced urinary tract carcinogenesis". Carcinogenesis, 1995, 16, 1493.

[9] Rao K., Detrisan C., Steele V., Hawk E., Kelloff G., McCormick D.: "Differential activity of aspirin, ketoprofen and sulindac as cancer chemo preventive agents in the mouse urinary bladder" Carcinogenesis, 1996, 17, 1435.

[10] Okajima E, Denda A, Ozono S, Takahama M, Akai H, Sasaki Y et al. Chemo preventive effects of nimesulide, a selective COX-2 inhibitor, on the development of rat urinary bladder carcinomas inhibiated by N-butyl-N-4-hydroxyburosamine. Cancer Res 1998; 58: 3028-3031.

[11] Lynch P.M.: "COX-2 inhibition in clinical cancer prevention". Oncology, 2001, 15 (suppl. 5), 21.

[12] Baldus S.E., Zibes T.K., Engel S., Hanisch F.G., Monig S.P., Lorenzo J.: "Correlation of immunohistochemical reactivity of mucin peptide cores MUCl and MUC2 with the histopathological subtype and prognosis of gastric carcinomas". Int. J. Cancer, 1998, 79, 133.

[13] Smith W.L., DeWitt D.L., Garavito R.M.: "Cyclooxygenases: structural, cellular, and molecular biology". Annu. Rev. Biochem., 2000, 69, 145.

[14] Vane J.R., Bakhle Y.S., Botting R.M.: "Cyclooxygenase I and 2" Annu. Rev. Pharmacol. Toxicol., 1998, 38, 97.

[15] Hla T., Bishop-Bailey D., Liu C.H., Schaefers H.J., Trifan O.C "Cyclooxygenase 1 and 2 isoenzymes". Int. J. Biochem. Cell Biol., 1999, 31, 551.

[16] Funk C.D., F unk L.B., Kennedy M.E., Pong A.S., F itzGerald G.A.: "Human platelet/erthroleukemia cell prostaglandin G/H synthase". FASEB J., 1991, 5, 2304.

[17] Jones D.A., Carlton D.P., McIntyre T.M., Zimmerman G.A., Prescott S.M.: "Molecular cloning of human prostaglandin endoperoxide synthase type II and demonstration of expression in response to cytokines". J. Biol. Chem., 1993, 268, 9049.

[18] Liu C.H., Chang S.H., Narko K., Trifan O.C., Wu M.T., Smith E., Haudenschild C., Lane T.F., Hla T.: "Overexpression of COX-2 is sufficient enough to induce turnorogenesis in transgenic mice". J. BioI. Chem., 2001, 25,276, 18563.

[19] Oshima M., Dinchuk J.E., Kargman S.L., Oshima H., Hancock B., Kwong E., Trazaskos J.M., Evans J.F., Taketo M.M.: "Suppression of intestinal polyposis in Apc delta 716 knockout mice by inhibition of cyclooxygenase 2". Cell, 1996, 87, 803.

[20] DuBois R.N., Radhika A., Reddy B.S., Entingh A.J.: "Increased cyclooxygenase-2 levels in carcinogen-induced rat colonic tumors". Gastroenterology, 1996, 110, 1259.

[21] Hwang D., Scollard D., Byrne J., Levine E.: "Expression of cyclooxygenase-1 and -2 in human breast cancer". J. Natl. Cancer Inst., 1998, 90, 455.

[22] Soslow R.A., Dannenberg A.J., Rush D., Woerner B.M., Khan K.N., Masferrer J., Koki A.T.: "COX-2 is expressed in human pulmonary, colonic and mammary tumors". Cancer, 2000, 89, 2637.

[23] T hun M.J.: "NSAID use and decreased risk of gastrointestinal cancers". Gastroenterol. Clin. North Am., 1996, 25, 333.

[24] Williams C.S., Mann M., DuBois R.N.:'The role of cyclooxygenases in inflammation, cancer and development". Oncogene, 1999, 18, 7908.

[25] Bokhman J.V.: "Two pathogenetic types of endometrial carcinoma". Gynecol. Oneal., 1983, 15, 10.

[26] Robboy S.J., Bradley R.: "Changing trends and prognostic features in endometrial cancer associated with exogenous estrogen therapy". Obstet. Gynecol., 1979, 54, 269.

[27] Zhao-Y., Agarwal V.R., Mendelson C.R., Simpson E.R.: "Estrogen biosynthesis proximal to a breast tumor is stimulated by PGE2 via cAMP, leading to activation of promoter II of the CYP19 (aromatase) gene". Endocrinology, 1996, 137, 5739.

[28] Bulun S.E., Zeitoun K.M., Takayama K., Sasano H.: "Estrogen biosynthesis in endometriosis: molecular basis and clinical relevance". J. Mol. End., 2000, 25, 35.

[29] Zeitoun K., Takayama K., Michael M.D., Bulun S.E.: "Stimulation of aromatase P450 promoter (II) activity in endometriosis and its inhibition in endometrium are regulated by competitive binding of steroidogenic factor- I and chicken ovalbumin upstream promoter transcription factor to the same cis-acting element". Mol. Endocrinol., 1999, 13, 239.

[30] Tamura M., Sebastian S., Yang S., Gurates B., F errer K., Sasano H., Okamura K., Bulun S.E.: "Up-regulation of cyclooxygenase-2 expression and prostaglandin synthesis in endometrial stromal cells by malignant endometrial epithelial cells. A paracrine effect mediated by prostaglandin E2 and nuclear factor-kappa B". J. Biol. Chem., 2002, 19, 277, 26208.

[31] Richards J.A., Petrel T.A., Brueggemeier R.W.: "Signaling pathways regulating aromatase and cyclooxygenases in normal and malignant breast cells". J. Ster. Biochem. Mol. Biol., 2002, 80, 203.

[32] Brodie A.M.H., Lu Q., Long B.J., Fulton A., Chen T., Macpherson N. et al.: "Aromatase and COX-2 expression in human breast cancers". J. Ster. Biochem. Mo/. Biol., 2001, 79, 41.

[33] Landen C.N. Jr., Mathur S.P., Richardson M.S., Creasman W.T "Expression of cyclooxygenase-2 in cervical, endometrial, and ovarian malignancies". Am. J. Obstet. Gynecol., 2003, 188, 1174

[34] Uotila P.J., Erkkola R.U., Klemi P.J.: "The expression of cyclooxygenase-1 and -2 in proliferative endometrium and endometrial adenocarcinoma". Ann. Med., 2002, 34, 428.

[35] Ferrandina G., Legge F., Ranelletti F.O., Zannoni G.F., Magg,ano N., Evangelisti A. et al.: "Cyclooxygenase-2 expression in endometrial carcinoma: correlation with clinicopathologic parameters and clinical outcome". Cancer, 2002, 95, 801.

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