The Prognostic Importance of EGFR and COX-2 Expression in Cervix Cancer Stages IIb-IVa


Objectives. Locally advanced cervix cancer represents a therapeutic challenge with a delicate balance between effect and toxicity. Consequently, there is an obvious need for new prognostic parameters with a perspective of a more individualized treatment. The aim of the present study was to evaluate the possible prognostic importance of epidermal growth factor receptor and cyclooxygenase-2 expression in locally advanced cervix cancer. Methods. The study included 91 patients with cervix cancer, FIGO stages IIb-IVa, and were treated with curative intent according to the Nordic Cervix Cancer protocol (NOCECA). The median observation time was 7 years. Epidermal growth factor receptor and cyclooxygenase-2 expression was evaluated by immunohistochemistry using commercially available antibodies. The tumor marker expression was evaluated according to a semi-quantitative scoring system with a positive score when more than 10% of the tumor cells were moderately or strongly stained. Results. Epidermal growth factor receptor and cyclooxygenase-2 over-expression was found in 22% and 18% of the patients, respectively. The survival differed according to epidermal growth factor receptor and cyclooxygenase-2 over-expression as calculated by Kaplan-Meier plots and log-rank test (p = 0.0002 and p = 0.0084 respectively). A multivariate Cox Regression analysis identified each tumor marker as an independent prognostic factor. Conclusion. The results clearly indicate epidermal growth factor receptor and cyclooxygenase-2 hold important prognostic information, markedly appearing with a long-term observation. We found that both parameters were independent prognostic factors, and to further clarify this matter our retrospective analysis should be confirmed in a prospective study with more patients.

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P. Adimi, K. Steffensen, D. Schledermann, E. Rasmussen and A. Jakobsen, "The Prognostic Importance of EGFR and COX-2 Expression in Cervix Cancer Stages IIb-IVa," Journal of Cancer Therapy, Vol. 2 No. 1, 2011, pp. 9-15. doi: 10.4236/jct.2011.21002.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] C. Vale, J. F. Tierney, L. A. Stewart, M. Brady, K. Dinshaw, A. Jakobsen, et al., “Reducing Uncertainties about the Effects of Chemoradiotherapy for Cervical Cancer: A Systematic Review and Meta-Analysis of Individual Patient Data from 18 Randomized Trials,” Journal Clinical Oncology, Vol. 26, No. 35, December 2008, pp. 5802- 5812. doi:10.1200/JCO.2008.16.4368
[2] W. J. Gullick, “Prevalence of Aberrant Expression of the Epidermal Growth Factor Receptor in Human Cancers,” British Medical Bulletin, Vol. 1, No. 47, January 1991, pp. 87-98.
[3] J. W. Kim, Y. T. Kim, D. K. Kim, C. H. Song and J. W. Lee, “Expression of Epidermal Growth Factor Receptor in Carcinoma of the Cervix,” Gynecologic Oncology, Vol. 2, No. 60, February 1996, pp. 283-287. doi:10.1006/gyno.1996.0039
[4] W. R. Hanson and C. Thomas, “16, 16-Dimethyl ProsTaglandin E2 Increases Survival of Murine Intestinal Stem Cells When Given before Photon Radiation,” Radiat Research, Vol. 2, No. 96, November 1983, pp. 393-398. doi:10.2307/3576222
[5] J. L. Young, A. A. Jazaeri, C. J. Darus and S. C. Modesitt, “Cyclooxygenase-2 in Cervical Neoplasia: A Review,” Gynecologic Oncology, Vol. 1, No. 109, April 2008, pp. 140-145. doi:10.1016/j.ygyno.2008.01.008
[6] A. M. Kersemaekers, G. J. Fleuren, G. G. Kenter, L. J. Van den Broek, S. M. Uljee, J. Hermans, et al., “Oncogene Alterations in Carcinomas of the Uterine Cervix: Overexpression of the Epidermal Growth Factor Receptor is Associated with Poor Prognosis,” Clinical Cancer Research, Vol. 3, No. 5, March 1999, pp. 577-586.
[7] G. B. Kristensen, R. Holm, V. M. Abeler and C. G. Trope, “Evaluation of the Prognostic Significance of Cathepsin D, Epidermal Growth Factor Receptor and c-erbB-2 in Early Cervical Squamous Cell Carcinoma. An ImmunoHistochemical Study,” Cancer, Vol. 3, No. 78, August 1996, pp. 433-440. doi:10.1002/(SICI)1097-0142(19960801)78:3<433::AID-CNCR9>3.0.CO;2-K
[8] F. Baltazar, A. L. Filho, C. Pinheiro, M. A. Moreira, G. S. Queiroz, G. J. Oton, A. F. Júnior, L. F. Ribeiro and F. C. Schmitt, “Cyclooxygenase-2 and Epidermal Growth Factor Receptor Expressions in Different Histological Subtypes of Cervical Carcinomas,” International Journal of Gynecologic Pathology, Vol. 3, No. 26, July 2007, pp. 235-241. doi:10.1097/pgp.0b013e31802f1996
[9] T. Manchana, S. Triratanachat, N. Sirisabya and A. Vasuratna, W. Termrungruanglert and D. Tresukosol, “Prevalence and Prognostic Significance of COX-2 Expression in Stage IB Cervical Cancer,” Gynecologic Oncology, Vol. 3, No. 100, March 2006, pp. 556-560. doi:10.1016/j.ygyno.2005.09.014
[10] N. Singh and S. Arif, “Histopathologic Parameters of Prognosis in Cervical Cancer—A Review,” International Journal of Gynecologic Cancer, Vol. 5, No. 14, September-October 2004, pp. 741-750. doi:10.1111/j.1048-891X.2004.014504.x
[11] G. Scambia, G. Ferrandina, M. Distefano, G. D’Agostino, P. Edetti-Panic and S. Mancuso, “Epidermal Growth Factor Receptor (EGFR) is not Related to the Prognosis of Cervical Cancer,” Cancer Letter, Vol. 2, No. 123, January 1998, pp. 135-139. doi:10.1016/S0304-3835(97)00421-7
[12] A. K. Lindstr?m, T. Tot, U. Stendahl, S. Syrj?nen, K. Syrj?nen and D. Hellberg, “Discrepancies in Expression and Prognostic Value of Tumor Markers in Adenocarcinoma and Squamous Cell Carcinoma in Cervical Cancer,” Anticancer Research, Vol. 7, No. 29, July 2009, pp. 2577- 2578.
[13] Y. B. Kim, G. E. Kim, N. H. Cho, H. R. Pyo, S. J. Shim, S. K. Chang, et al., “Overexpression of Cyclooxygenase-2 is Associated with a Poor Prognosis in Patients with Squamous Cell Carcinoma of the Uterine Cervix Treated with Radiation and Concurrent Chemotherapy,” Cancer, Vol. 3, No. 95, 2002, pp. 531-539. doi:10.1002/cncr.10684
[14] G. E. Kim, Y. B. Kim, N. H. Cho, H. C. Chung, H. R. Pyo, J. D. Lee, et al., “Synchronous Coexpression of Epidermal Growth Factor Receptor and Cyclooxygenase-2 in Carcinomas of the Uterine Cervix: A Potential Predictor of Poor Survival,” Clinical Cancer Research, Vol. 4, No. 10, February 2004, pp. 1366-1374. doi:10.1158/1078-0432.CCR-0497-03
[15] H. Ishikawa, T. Ohno, S. Kato, M. Wakatsuki, M. Iwakawa, T. Ohta et al., “Cyclooxygenase-2 Impairs Treatment Effects of Radiotherapy for Cervical Cancer by Inhibition of Radiation-Induced Apoptosis,” International Journal of Radiation Oncology Biology Physics, Vol. 3, No. 66, December 2006, pp. 1347-1355. doi:10.1016/j.ijrobp.2006.07.007
[16] T. W. Davis, N. Hunter, O. C. Trifan, L. Milas and J. L. Masferrer, “COX-2 Inhibitors as Radio Sensitizing Agents for Cancer Therapy,” American Journal of Clinical Oncology, Vol. 4, No. 26, August 2003, pp. 58-61. doi:10.1097/01.COC.0000074158.59269.9F
[17] F. G. Herrera, P. Chan, C. Doll, M. Milosevic, A. Oza, A. Syed, et al., “A Prospective Phase I-II Trial of the Cyclooxygenase-2 Inhibitor Celecoxib in Patients with Carcinoma of the Cervix with Biomarker Assessment of the Tumor Microenvironment,” International Journal of Radiation Oncology Biology Physics, Vol. 1, No. 67, January 2007, pp. 97-103. doi:10.1016/j.ijrobp.2006.08.024
[18] D. K. Gaffney, K. Winter, A. P. Dicker, B. Miller, P. J. Eifel, J. Ryu, et al., “A Phase II Study of Acute Toxicity for Celebrex (celecoxib) and Chemo Radiation in Patients with Locally Advanced Cervical Cancer: Primary Endpoint Analysis of RTOG 0128,” International Journal of Radiation Oncology Biology Physics, Vol. 1, No. 67, January 2007, pp. 104-109. doi:10.1016/j.ijrobp.2006.08.002
[19] A. Jakobsen, J. P. Mortensen, C. Bisgaard, J. Lindebjerg, S. R. Rafaelsen and V. O. Bendtsen, “A COX-2 Inhibitor Combined with Chemoradiation of Locally Advanced Rectal Cancer: A Phase II Trial,” International Journal of Gynecologic Pathology, Vol. 3, No. 23, March 2008, pp. 251-255. doi:10.1007/s00384-007-0407-7
[20] S. Bellone, G. Frera, G. Landolfi, C. Romani, E. Bandiera, G. Tognon, J. J. Roman, A. F. Burnett, S. Pecorelli and A. D. Santin, “Over Expression of Epidermal Growth Factor Type-1 Receptor (EGF-R1) in Cervical Cancer: Implications for Cetuximab-Mediated Therapy Inrecurrent/Me- tastatic Disease,” Gynecology Oncology, Vol. 3, No. 106, September 2007, pp. 513-520. doi:10.1016/j.ygyno.2007.04.028
[21] E. S. Kim, F. R. Khuri and R. S. Herbst, “Epidermal Growth Factor Receptor Biology (IMC-C225),” Current Opinion Oncology, Vol. 6, No. 13, November 2001, pp. 506-513. doi:10.1097/00001622-200111000-00014
[22] J. M. Del Campo, A. Prat, A. Gil-Moreno, J. Perez and M. Parera, “Update on Novel Therapeutic Agents for Cervical Cancer,” Gynecologic Oncology, Vol. 3 (Suppl. 2), No. 110, September 2008, pp. 72-76.
[23] K. Liang, K. K. Ang, L. Milas, N. Hunter and Z. Fan, “International Journal of Radiation Oncology Biology,” Physics, Vol. 1, No. 57, 2003, pp. 246-254. doi:10.1016/S0360-3016(03)00511-X

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