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Expression of Cox-2 and Bcl-2 in Paget's Disease of the Breast

  • Alikanoglu, Arsenal Sezgin (Department of Pathology, Antalya Education and Research Hospital) ;
  • Yildirim, Mustafa (Department of Medical Oncology, Ministry of Health Batman Regional Goverment Hospital) ;
  • Suren, Dinc (Department of Medical Oncology, Ministry of Health Batman Regional Goverment Hospital) ;
  • Tutus, Birsel (Department of Pathology, Ministry of Health Finike Regional Goverment Hospital) ;
  • Kaya, Vildan (Department of Radiation Oncology, Suleyman Demirel University) ;
  • Topal, Cumhur Selcuk (Department of Pathology, Umraniye Education and Research Hospital) ;
  • Keser, Sevinc (Department of Pathology, Kartal Education and Research Hospital) ;
  • Karadayi, Ayse Nimet (Department of Pathology, Kartal Education and Research Hospital) ;
  • Kapucuoglu, Fatma Nilgun (Department of Pathology, Suleyman Demirel University) ;
  • Ayva, Sebnem (Department of Pathology, Baskent University) ;
  • Gunduz, Seyda (Department of Medical Oncology, Antalya Education and Research Hospital)
  • 발행 : 2015.03.04

초록

Background: Paget's disease (PD) is a rare form of intraepithelial adenocarcinoma that involves breast and extramammarian tissues. It is often associated with ductal carcinoma in situ and/or invasive ductal cancer. Molecular pathways that play a role in development of Paget's disease are stil unclear. Expression patterns of Cox-2 and bcl-2 were therefore assessed. Materials and Methods: Patients with a histopathological diagnosis of Paget's disease were included in this study. Patient files were analysed retrospectively. Results: Invasive cancer was diagnosed in 35 (76.1%) of the patients, 7 (15.2%) had ductal carcinoma in situ and 4 (8.7%) patients had no associated neoplasm. Twenty four (52.2%) patients showed COX-2 expression in Paget cells whereas no expression was seen in 22 (47.8%) patients. No relation was found between COX-2 expression and the lesion underlying Paget's disease (p=0.518). Bcl-2 expression in Paget cells was found positive in 12 (26.1%) and negative in 27 (58,7%) cases. There was no relation between Bcl-2 expression and the lesion accompanying Paget's disease (p=0.412). No relation was observed between COX-2 expression and Bcl-2 expression (p=0.389). Conclusions: In breast cancer, COX-2 expression is associated with poor prognostic factors. As COX-2 expression increases the tendency to metastasize also increases. In our study we found a significantly high COX-2 expression in Paget's disease of the breast. We suggest that COX-2 expression and inflammatory processes may play a role in pathogenesis of the Paget's disease of the breast.

키워드

참고문헌

  1. Alikanoglu AS, Yildirim M, Suren D, et al(2013). Bcl-2 and Ki-67 expression in young women with breast cancer. J Clin Anal Med, 4, 386-9. https://doi.org/10.4328/JCAM.1110
  2. Ashikari R, Park K, Huvos AG, Urban JA (1970). Paget's disease of the breast. Cancer, 26, 680-5. https://doi.org/10.1002/1097-0142(197009)26:3<680::AID-CNCR2820260329>3.0.CO;2-P
  3. Chen CY, Sun LM, Anderson BO (2006). Paget disease of the breast: changing patterns of incidence, clinical presentation, and treatment in the US. Cancer, 107, 1448-58. https://doi.org/10.1002/cncr.22137
  4. Cohen C, Guarner J, De Rose PB (1993). Mammary Paget's disease and associated carcinoma. An immunohistochemical study. Arch Pathol Lab Med, 117, 291-4.
  5. Costa C, Soares R, Reis-Filho JS, et al (2002). Cyclo-oxygenase 2 expression is associated with angiogenesis and lymph node metastasis in human breast cancer. J Clin Pathol, 55, 429-34. https://doi.org/10.1136/jcp.55.6.429
  6. Darb-Esfahani S, Loibl S, Müller BM, et al (2009). Identification of biology-based breast cancer types with distinct predictive and prognostic features: role of steroid hormone and HER2 receptor expression in patients treated with neoadjuvant anthracycline/taxane-based chemotherapy. Breast Cancer Res, 11, 69. https://doi.org/10.1186/bcr2363
  7. Davies G, Martin LA, Sacks N, Dowsett M (2002). Cyclooxygenase -2 (COX-2), aromatase and breast cancer: a possible role for COX-2 inhibitors in breast cancer chemoprevention. Ann Oncol, 13, 669-78 https://doi.org/10.1093/annonc/mdf125
  8. Denkert C, Winzer KJ, Muller BM, et al (2003). Elevated expression of cyclooxygenase-2 is a negative prognostic factor for disease free survival and overall survival in patients with breast carcinoma. Cancer, 97, 2978-87. https://doi.org/10.1002/cncr.11437
  9. El-Mageed AA, Mohamed AES and Elesawy BH (2013) Different Prognostic Factors Correlate with Bcl-2 Expression among Triple Negative and Non-Triple Negative Breast Cancers. Asian Pac J Cancer Prev, 14, 1037-41. https://doi.org/10.7314/APJCP.2013.14.2.1037
  10. Evans JF, Kargman SL (2004). Cancer and Cyclooxygenase -2 (COX-2) inhibition. Curr Pharm Des, 10, 627-34. https://doi.org/10.2174/1381612043453126
  11. Hanna W, Alowami S, Malik A (2003). The role of HER-2/neu oncogene and vimentin filaments in the production of the Paget's phenotype. Breast J, 9, 485-90. https://doi.org/10.1046/j.1524-4741.2003.09610.x
  12. Half E, Tang XM, Gwyn K, et al (2002). Cyclooxygenase-2 expression in human breast cancers and adjacent ductal carcinoma in situ. Cancer Res, 15, 1676-81.
  13. Horn LC, Purz S, Krumpe C, Bilek K (2008). COX-2 and Her-2/ neu are overexpressed in Paget's disease of the vulva and the breast: results of a preliminary study. Arch Gynecol Obstet, 277, 135-8. https://doi.org/10.1007/s00404-007-0434-1
  14. Ihemelandu CU, Dewitty RL, Leffall LD, Suryanarayana SM, Frederick WA (2009). Clinical significance of p53 and bcl-2 protein coexpression phenotypes in molecular breast cancer subtypes of pre-menopausal and post-menopausal African- American women. Am Surg, 75, 776-84.
  15. Jaafar H, Abdullah S, Murtey MD, Idris FM (2012) Expression of Bax and Bcl-2 in tumour cells and blood vessels of breast cancer and their association with angiogenesis and hormonal receptors. Asian Pacific J Cancer Prev, 13, 3857-62 https://doi.org/10.7314/APJCP.2012.13.8.3857
  16. Jahn H, Osther PJ, Nielsen EH, Rasmussen G, Andersen J (1995). An electron microscopic study of clinical Paget's diseaese of the nipple. APMIS, 103, 628-34. https://doi.org/10.1111/j.1699-0463.1995.tb01415.x
  17. Karakas C (2011). Paget's disease of the breast. J Carcinog, 10, 100-108.
  18. Kim HS, Moon HG, Han W, et al (2012). COX2 overexpression is a prognostic marker for Stage III breast cancer. Breast Cancer Res Treat, 132, 51-9. https://doi.org/10.1007/s10549-011-1521-3
  19. Kirkina V, Joos S, Zo M (2004). The role of Bcl-2 family members in tumorigenesis. Biochim Biophys Acta, 1644, 229-49 https://doi.org/10.1016/j.bbamcr.2003.08.009
  20. Lester T, Wang J, Bourne P, et al (2009). Different Panels of Markers Should Be Used to Predict Mammary Paget's Disease Associated with In Situ or Invasive Ductal Carcinoma of the Breast. Ann Clinical Laboratory Science, 39, 17-24.
  21. Li Xiang, Shiqi Wang, Xianqing Jin, et al (2012). Expression of BMP2, TLR3, TLR4 and COX2 in colorectal polyps, adenoma and adenocarcinoma. Molecular Medicine Reports, 6, 973-6.
  22. Masferrer JL, Leahy KM, Koki AT, et al (2000). Antiangiogenic and antitumor activities of cyclooxygenase-2 inhibitors. Cancer Res, 60, 1306-11.
  23. Meissner K, Rivière A, Haupt G, Löning T (1990). Study of Neuprotein expression in mammary Paget's disease with and without underlying breast carcinoma and in extramammary Paget's disease. Am J Pathol, 137, 1305-9.
  24. Mohammad AM, Abdel HA, Abdel W et al (2006). Expression of cyclooxygenase-2 and 12-lipoxygenase in human breast cancer and their relationship with HER-2/neu and hormonal receptors: Impact on prognosis and therapy. Indian J Cancer, 43, 163-8. https://doi.org/10.4103/0019-509X.29421
  25. Muir R (1939). Further observations on Paget's disease of the nipple and associated lesions. J Pathol, 49, 299-312. https://doi.org/10.1002/path.1700490204
  26. O'Byrne KJ, Dalgleish AG (2001). Chronic immune activation and inflammation as the cause of malignancy. Br J Cancer, 85, 473-483. https://doi.org/10.1054/bjoc.2001.1943
  27. Ortiz-Pagan S, Cunto-Amesty G, Narayan S, et al (2011). Effect of Paget's disease on survival in breast cancer: an exploratory study. Arch Surg, 46, 1267-70.
  28. Paget J (1874). On the disease of mammary areola preceding cancer of the mammary gland. St Bartholomews Hosp Rep, 10, 87-89.
  29. Rhee J, Han SW, Oh DY, et al (2008). The clinicopathologic characteristics and prognostic significance of triplenegativity in node-negative breast cancer. BMC Cancer, 8, 307. https://doi.org/10.1186/1471-2407-8-307
  30. Rostamizadeh L, Fakhrjou A, Montazeri V, et al (2013) Bcl-2 gene expression in human breast cancers in Iran. Asian Pac J Cancer Prev, 14, 4209-14. https://doi.org/10.7314/APJCP.2013.14.7.4209
  31. Sagami S (1963). Electron microscopic studies in Paget's disease. Med J Osaka Univ, 14, 173-88.
  32. Silvestrini R, Veneroni S, Daidone MG, et al (1994). The Bcl-2 protein: a prognostic indicator strongly related to p53 protein in lymph node-negative breast cancer patients. J Natl Cancer Inst, 86, 499-504. https://doi.org/10.1093/jnci/86.7.499
  33. Smith WL, DeWitt DL, Garavito RM (2000). Cyclooxygenases: structural, cellular and molecular biology. Annu Rev Biochem, 69, 145-82. https://doi.org/10.1146/annurev.biochem.69.1.145
  34. Tawfik K, Kimler BF, Davis MK, Fan F, Tawfik O (2012). Prognostic significance of Bcl-2 in invasive mammary carcinomas: a comparative clinicopathologic study between "triple-negative" and non-"triple-negative" tumors. Hum Pathol, 43, 23-30. https://doi.org/10.1016/j.humpath.2011.04.011
  35. Yu B, Sun X, Shen HY, et al (2010). Expression of the apoptosisrelated genes BCL-2 and BAD in human breast carcinoma and their associated relationship with chemosensitivity. J Exp Clin Cancer Res, 29, 107. https://doi.org/10.1186/1756-9966-29-107
  36. Zheng S, Song QK, Zhao L, et al. (2013) Characteristics of mammary Paget's disease in China: a national-wide multicenter retrospective study during 1999- 2008 . Asian Pac J Cancer Prev, 13, 1887-93 .
  37. Zhang GJ, Kimijima I, Abe R, et al (1997). Correlation between the expression of apoptosis-related bcl-2 and p53 oncoproteins and the carcinogenesis and progression of breast carcinomas. Clin Cancer Res, 3, 2329-35.
  38. Witton CJ, Hawe SJ, Cooke TG, Bartlett JM (2004). Cyclooxygenase -2 (COX-2) expression is associated with poor outcome in ER-negative, but not ER-positive , breast cancer. Histopathology, 45, 47-54. https://doi.org/10.1111/j.1365-2559.2004.01898.x