Skip to main content

Advertisement

SpringerLink
Log in

Correlation of cyclooxygenase-2 and aromatase immunohistochemical expression in invasive ductal carcinoma, ductal carcinoma in situ, and adjacent normal epithelium

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Summary

The purpose of our study was to evaluate the correlation between cyclooxygenase-2 (COX-2) and aromatase immunohistochemical expression in ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) present in the same breast, as well as in adjacent stroma and normal epithelium, we still correlated with nuclear grade, histologic grade, presence or absence of comedonecrosis, tumor size, and age at diagnosis. Forty-seven cases were evaluated through the use of anti-aromatase and anti-COX-2 polyclonal antibodies. Making the correlation of COX-2 and aromatase expression, we observed that COX-2 expression in IDC was correlated with aromatase expression in IDC (p<0.001), DCIS (p<0.001), normal epithelium (p=0.024), and stroma tumor (p<0.001). When the correlation was made between COX-2 expression in DCIS with aromatase, we observed positive correlation in IDC (p<0.001), DCIS (p<0.001), normal epithelium (p=0.013), and stroma tumor (p<0.001). In the correlative analysis of COX-2 expression in normal epithelium with aromatase in different evaluated tissues, we observed the following statistical results: IDC (p<0.001), DCIS (p<0.001), normal epithelium (p=0.005), and stroma tumor (p=0.047). Our results demonstrate the high correlation between COX-2 and aromatase expression in IDC, DCIS and normal epithelium, showing the importance of these two enzymes in the induction, promotion and progression of breast cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Purohit A, Newman SP, Reed MJ, The role of cytoquines in regulating estrogen synthesis: implications for the etiology of breast cancer Breast Cancer Res 4: 65–69 2002

    Article  PubMed  CAS  Google Scholar 

  2. Reed MJ, Coldham NG, Patel SR, Interleukin-1 and Interleukin-6 in breast cyst fluid: their role in regulating aromatase activity in breast cancer cells J Endocrinol 132: 5–8, 1992

    Article  Google Scholar 

  3. Singh A, Purohit A, Ghilchik MW, Reed MJ, The regulation of aromatase activity in breast fibroblasts: the role of Interleukin-6 and prostaglandin E2 Endocr Relat Cancer 6: 139–147, 1999

    Article  PubMed  CAS  Google Scholar 

  4. Brueggemeier RW, Quinn AL, Parret ML, Joarder FS, Harris RE, Robertson FM, Correlation of aromatase and cyclooxygenase gene expression in human breast cancer specimens Cancer Lett 140: 27–35, 1999

    Article  PubMed  CAS  Google Scholar 

  5. Richards JA, Brueggemeier RW, Prostaglandin E2 Regulates Aromatase Activity and Expression in Human Adipose Stromal Cells via Two Distinct Receptor Subtypes J Clin Endocrinol Metab 88(6): 2810–2813, 2003

    Article  PubMed  CAS  Google Scholar 

  6. Davies G, Martin L, Sacks N, Dowset M, Cyclooxygenase-2 (COX-2), aromatase and breast cancer; a possible role for COX-2 inhibitors in breast cancer chemoprevention Ann Oncol 13: 669–678, 2002

    Article  PubMed  CAS  Google Scholar 

  7. Díaz-Cruz ES, Shapiro CL, Brueggemeier RW, Cyclooxygenase inhibitors suppress aromatase expression and activity in breast cancer cells J Clin Endocrinol Metab 90: 2563–2570, 2005

    Article  PubMed  CAS  Google Scholar 

  8. Clyne CD, Speed CJ, Zhou J, Simpson ER, Liver receptor homologue-1 (LRH-1) regulates expression of aromatase in preadipocites J Biol Chem 227(23): 20591–20597, 2002

    Article  CAS  Google Scholar 

  9. Zhou J, Suzuki T, Kovacic A, Saito R, Miki Y, Ishida T, et al. Interactions between prostaglandin E(2), liver receptor homologue-1, and aromatase in breast cancer Cancer Res 65(2): 657–663, 2005

    PubMed  CAS  Google Scholar 

  10. Brodie AM, Lu Q, Long BJ, Fulton A, Chen T, Macpherson N, et al. Aromatase and COX-2 expression in human breast cancers J Steroid Biochem Mol Biol. 79(1–5): 41–47, 2001

    Article  PubMed  CAS  Google Scholar 

  11. Dabbs DJ, Ductal carcinoma of the breast: nuclear grade as a predictor of S-phase fraction Human Pathol 24(6): 251–256, 1993

    Google Scholar 

  12. Elston CW, Ellis IO, Pathological prognostic factors in breast cancer I.The value of histological grade in breast cancer: experience from a large study with long-term follow-up Histopathology 19: 403–410, 1991

    Article  PubMed  CAS  Google Scholar 

  13. Ristimäki A, Sivula A, Lundin J, Prognostic significance of elevated cyclooxygenase-2 expression in breast cancer Cancer Res 62:632–635, 2002

    PubMed  Google Scholar 

  14. Shim V, Gauthier ML, Sudilovsky D, Mantei K, Chew KL, Moore DH, et al. Cyclooxygenase-2 expression is related to nuclear grade in ductal carcinoma in situ and is increased in its normal adjacent epithelium Cancer Res 63: 2347–2350, 2003

    PubMed  CAS  Google Scholar 

  15. Boland GP, Butt IS, Prasad R, Knox WF, Bundred NJ, COX-2 expression is associated with an aggressive phenotype in ductal carcinoma in situ Br J Cancer 90: 423–429, 2004

    Article  PubMed  CAS  Google Scholar 

  16. Fisher B, Costantino JP, Wickerham DL, Redmond CK, Kavanah M, Cronin WM, Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study J Natl Cancer Inst 90: 1371–1388, 1998

    Article  PubMed  CAS  Google Scholar 

  17. Powles T, Eeles R, Ashley SE, Easton D, Chang J, Dowsett L, Interim analysis of the incidence of breast cancer in the Royal Marsden Hospital tamoxifen randomized chemoprevention trial Lancet 352: 98–101, 1998

    PubMed  CAS  Google Scholar 

  18. Veronesi U, Maisonneuve P, Sacchini V, Rotmensz N, Boyle P, Tamoxifen for breast cancer among hysterectomised women Lancet 359: 1122–1124, 2002

    Article  PubMed  CAS  Google Scholar 

  19. ATAC trialists’ Group. Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years adjuvant treatment for breast cancer. Lancet 365: 60–62, 2005

    Google Scholar 

  20. Hawk ET, Viner JL, Asad Umar A, William F, Anderson WF, Sigman CC, et al. Development of COX inhibitors in cancer prevention and therapy Am J Cancer 2: 27–55, 2003

    Article  CAS  Google Scholar 

  21. Buskens CJ, Sivula A, Van Ress BP, Haglund C, Offerhaus GJA, Van Lanschot JJb, et al. Comparison of cyclooxygenase 2 expression in adenocarcinomas of the gastric cardia and distal oesophagus Gut 52:1678–1683, 2003

    Article  PubMed  CAS  Google Scholar 

  22. Terry MB, Gammon MD, Zhang FF, Tawfik H, Teitelbaunm SL, Britton JA, et al. Association of frequency and duration of aspirin use and hormone receptor status with breast cancer risk JAMA 291(20): 2433–2440, 2004

    Article  PubMed  CAS  Google Scholar 

  23. DuBois RM, Aspirin and breast cancer prevention. The estrogen conection JAMA 291(20): 2488–2489, 2004

    Article  PubMed  CAS  Google Scholar 

  24. Huang M, Stolina M, Sharma S, Non-small cell lung cancer cyclooxygenase- 2-dependent regulation of cytokine balance in lymphocytes and macrophages: up-regulation of interleukin 10 and down-regulation of interleukin 12 production Cancer Res 58(6): 1208–1216, 1998

    PubMed  CAS  Google Scholar 

  25. Half E, Tang XT, Gwyn K, Sahin A, Wathen K, Sinicrope FA, Cyclooxygenase-2 expression in human breast cancers and adjacent ductal carcinoma in situ Cancer Res 62: 1676–1681, 2002

    PubMed  CAS  Google Scholar 

  26. Jeong YS, Hee JA, Yog HL, Seung KK, Kiyog PL, Kiong SL, Overexpression of cyclooxygenase-2 is associated with breast carcinoma its poor prognostic factors Mod Pathol 16(12): 1199–1204, 2003

    Article  PubMed  Google Scholar 

  27. Davies G, Salter J, Hills M, Martin L, Sacks N, Dowset M, Correlation of cyclooxygenase-2 expression and angiogenesis in human breast cancer Clin Cancer Res 9:2652–2656, 2003

    Google Scholar 

  28. Tan KB, Yong WP, Putti TC, Cyclooxygenase-2 expression: a potential prognostic and predictive marker for high-grade ductal carcinoma in situ of the breast Histopathology 44: 24–28, 2004

    Article  PubMed  Google Scholar 

  29. Perrone G, Santini D, Vincenci B, Zagami M, La Cesa A, Bianchi A, et al. COX-2 expession in DCIS: correlation with VEGF, HER-2/neu, prognostic molecular markers and clinicopathological features Histopathology 46(5): 561–568, 2005

    Article  PubMed  CAS  Google Scholar 

  30. Howe LR, Subbaramaiah K, Brown AM, Dannenberg AJ, Cyclooxygenase-2: a target for prevention and treatment of breast cancer Endocr Relat Cancer 8: 97–114, 2001

    Article  PubMed  CAS  Google Scholar 

  31. Benoit V, Relic B, Leval X, Chariot A, Merville MP, Bours V, Regulation of HER-2 oncogene expression by cyclooxygenase-2 and prostaglandin E2 Oncogene 23: 1631–1635, 2004

    Article  PubMed  CAS  Google Scholar 

  32. Silva MC, Rowlands MG, Dowsett M, Gusterson B, McKinna JA, Fryatt I, Intratumoral aromatase as a prognostic factor in human breast carcinoma Cancer Res 49(10): 2588–2591, 1989

    PubMed  CAS  Google Scholar 

  33. Lipton A, Santen RJ, Santner SJ, Harvey HA, Sanders SI, Matthews YL, Prognostic value of breast cancer aromatase Cancer 70(7): 1951–1955, 1992

    Article  PubMed  CAS  Google Scholar 

  34. Miller WR, Forrest AP, Oestradiol synthesis from C19 steroids by human breast cancers Br J Cancer 33: 116–118, 1976

    PubMed  CAS  Google Scholar 

  35. De Jong PC, Blankenstein MA, Nortier JW, Slee PH, Van De Ven J, Van Gorp JM, et al. The relationship between aromatase in primary breast tumors and response to treatment with aromatase inhibitors in advanced disease J Steroid Biochem Mol Biol 87(2–3): 149–155, 2003

    Article  PubMed  CAS  Google Scholar 

  36. Lu Q, Nakmura J, Savino A, Yue W, Weisz J, Dabbs DJ, et al. Expression of aromatase protein and messenger ribonucleic acid in tumor epithelial cells and evidence of functional significance of locally produced estrogen in human breast cancers Endocrinology 137: 3061–3068, 1996

    Article  PubMed  CAS  Google Scholar 

  37. Zhang Z, Yamshita H, Toyama T, Hara Y, Omoto Y, Sugiura H, et al. Semi-quantitative immunohistochemical analysis of aromatase expression in cuctal carcinoma of the breast Breast Cancer Res Treat 74: 47–53, 2002

    Article  PubMed  CAS  Google Scholar 

  38. Yamamoto Y, Yamashita J, Toi M, Muta M, Nagai S, Hanai N, et al. immunohistochemical analysis of estrone sulfatase and aromatase in human breast cancer tissue Oncology Rep 10: 791–796, 2003

    CAS  Google Scholar 

  39. Santner SJ, Pauley RJ, Tait L, Kaseta J, Santen RJ, Aromatase activity and expression in breast cancer and benign breast tissue stromal cells J Clin Endoclinol Metab 82(1): 200–208, 1997

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Gynecology and Obstetric, Santa Casa de São Paulo, São Paulo, Brazil

    Vilmar Marques Oliveira & Sebastião Piato

  2. Santa Casa de São Paulo, São Paulo, Brazil

    Vilmar Marques Oliveira, Sebastião Piato & Maria Antonieta Longo Galvão Silva

  3. Department of Pathology, Santa Casa de São Paulo, São Paulo, Brazil

    Maria Antonieta Longo Galvão Silva

Authors
  1. Vilmar Marques Oliveira
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sebastião Piato
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Maria Antonieta Longo Galvão Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Vilmar Marques Oliveira.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Oliveira, V.M., Piato, S. & Silva, M.A.L.G. Correlation of cyclooxygenase-2 and aromatase immunohistochemical expression in invasive ductal carcinoma, ductal carcinoma in situ, and adjacent normal epithelium. Breast Cancer Res Treat 95, 235–241 (2006). https://doi.org/10.1007/s10549-005-9010-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-005-9010-1

Keywords

Search

Navigation