Cyclooxygenase-2 and human epidermal growth factor receptor type 2 (HER-2) expression simultaneously in invasive and in situ breast ductal carcinoma
Keywords:
Cyclooxygenase 2, Receptor, erbB-2, Breast neoplasms, Carcinoma, intraductal, noninfiltrating, Carcinoma, ductal, breastAbstract
CONTEXT AND OBJECTIVE: Cyclooxygenase-2 (COX-2) and human epidermal growth factor receptor type 2 (HER-2) are associated with tumorigenesis. Studies have shown that HER-2 can regulate COX-2 expression. The aim of this study was to evaluate the correlation between COX-2 and HER-2 expression in normal breast epithelium and in ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) present in the same breast. DESIGN AND SETTING: Cross-sectional study at the Mastology Unit of the Department of Gynecology and Obstetrics, Santa Casa de Misericórdia de São Paulo Hospital. METHODS: COX-2 and HER-2 were detected using immunohistochemistry on 100 tissue fragments. HER-2 ≥ +2 was subjected to fluorescence in situ hybridization (FISH). RESULTS: COX-2 expression was detected in 87%, 85% and 75% of IDC, DCIS and normal epithelium, respectively. HER-2 expression was detected in 34% of IDC and 34% of DCIS. COX-2 in DCIS correlated with HER-2 in IDC (P = 0.049) and DCIS (P = 0.049). COX-2 in normal epithelium correlated with HER-2 in IDC (P = 0.046) and DCIS (P = 0.046). COX-2 in IDC was not associated with HER-2 (P = 0.235). Comparison between COX-2 and HER-2 in DCIS showed that there was a statistically significant difference with regard to nuclear grades II and III and presence of comedonecrosis (P < 0.001). In IDC, there was significant expression with nuclear grades II and III and histological grade II (P < 0.001). CONCLUSIONS: Our findings provide evidence that HER-2 and COX-2 regulate each other.
Downloads
References
DuBois RN. Aspirin and breast cancer prevention: the estrogen connection. JAMA. 2004;291(20):2488-9.
Taketo MM. Cyclooxygenase-2 inhibitors in tumorigenesis (Part II). J Natl Cancer Inst. 1998;90(21):1609-20.
Soslow RA, Dannenberg AJ, Rush D, et al. COX-2 is expressed in human pulmonary, colonic, and mammary tumors. Cancer. 2000:89(12); 2637-45.
Singh B, Lucci A. Role of cyclooxygenase-2 in breast cancer. J Surg Res. 2002;108(1):173-9.
Tsuji S, Tsujii M, Kawano S, Hori M. Cyclooxygenase-2 upregulation as a perigenetic change in carcinogenesis. J Exp Clin Cancer Res. 2001;20(1):117-29.
Greenlee RT, Hill-Harmon MB, Murray T, Thun M. Cancer statistics, 2001. CA Cancer J Clin. 2001;51(1):15-36.
Sharpe CR, Collet JP, McNutt M, et al. Nested case-control study of the effects of non-steroidal anti-inflammatory drugs on breast cancer risk and stage. Br J Cancer. 2000;83(1):112-20.
Harris RE, Beebe-Donk J, Alshafie GA. Reduction in the risk of human breast cancer by selective cyclooxygenase-2 (COX-2) inhibitors. BMC Cancer. 2006;6:27.
Smith WL, Langenbach R. Why there are two cyclooxygenase isozymes. J Clin Invest. 2001;107(12):1491-5.
Thun MJ, Henley SJ, Patrono C. Nonsteroidal anti-inflammatory drugs as anticancer agents: mechanistic, pharmacologic, and clinical issues. J Natl Cancer Inst. 2002;94(4):252-66.
Borg A, Baldetorp B, Fernö M, et al. ERBB2 amplification in breast cancer with a high rate of proliferation. Oncogene. 1991;6(1):137-43.
Bertucci F, Borie N, Ginestier C, et al. Identification and validation of an ERBB2 gene expression signature in breast cancers. Oncogene. 2004;23(14):2564-75.
Dickson RB, Lippman ME. Oncogenes and suppressor genes. In: Harris JR, Lippman ME, Morrow M, Hellman S, editors. Diseases of the breast. 2nd edition. Philadelphia: Lippincott Williams & Wilkins; 2000. p. 281-302.
Pinkas-Kramarski R, Shelly M, Guarino BC, et al. ErbB tyrosine kinases and the two neuregulin families constitute a ligand-receptor network.
Mol Cell Biol. 1998;18(10):6090-101.
Borg A, Tandon AK, Sigurdsson H, et al. HER-2/neu amplification predicts poor survival in node-positive breast cancer. Cancer Res. 1990;50(14):4332-7.
Tandon AK, Clark GM, Chamness GC, Ullrich A, McGuire WL. HER-2/ neu oncogene protein and prognosis in breast cancer. J Clin Oncol. 1989;7(8):1120-8.
Adam L, Vadlamudi R, Kondapaka SB, et al. Heregulin regulates cytoskeletal reorganization and cell migration through the p21- activated kinase-1 via phosphatidylinositol-3 kinase. J Biol Chem. 1998;273(43):28238-46.
Subbaramaiah K, Norton L, Gerald W, Dannenberg AJ. Cyclooxygenase-2 is overexpressed in HER-2/neu-positive breast cancer: evidence for involvement of AP-1 and PEA3. J Biol Chem. 2002;277(21):18649-57.
Ristimäki A, Sivula A, Lundin J, et al. Prognostic significance of elevated cyclooxygenase-2 expression in breast cancer. Cancer Res. 2002;62(3):632-5.
Half E, Tang XM, Gwyn K, et al. Cyclooxygenase-2 expression in human breast cancers and adjacent ductal carcinoma in situ. Cancer Res. 2002;62(6):1676-81.
Brown PH, Subbaramaiah k, Salmon AP, et al. Combination chemoprevention of HER2/neu-induced breast cancer using a cyclooxygenase-2 inhibitor and a retinoid X receptor-selective retinoid. Cancer Prev Res (Phila). 2008;1(3):208-14.
Dabbs DJ. Ductal carcinoma of breast: nuclear grade as a predictor of S-phase fraction. Human Pathol. 1993;24(6):652-6.
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. 1991;19(5):403-10.
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. 2004;90(2):423-9.
Brower V. Feeding the flame: new research adds to role of inflammation in cancer development. J Natl Cancer Inst. 2005;97(4):251-3.
Flowers M, Thompson PA. t10c12 conjugated linoleic acid suppresses HER2 protein and enhances apoptosis in SKBr3 breast cancer cells: possible role of COX2. PLoS One. 2009;4(4):e5342.
Pikarsky E, Porat RM, Stein I, et al. NF-kappaB functions as a tumour promoter in inflammation-associated cancer. Nature. 2004;431(7007):461-6.
Balkwill F, Coussens LM. Cancer: an inflammation link. Nature. 2004;431(7007):405-6.
Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008;454(7203):436-44.
Zhou Y, Yau C, Gray JW, et al. Enhanced NF kappa B and AP-1 transcriptional activity associated with antiestrogen resistant breast cancer. BMC Cancer. 2007;7:59.
Dillon MF, Stafford AT, Kelly G, et al. Cyclooxygenase-2 predicts adverse effects of tamoxifen: a possible mechanism of role for nuclear HER2 in breast cancer patients. Endocr Relat Cancer. 2008;15(3):745-53.
Mohamed AM, Abdel HA, Abdel W, et al. 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. 2006:43(4):163-8.
Davies G, Salter J, Hills M, et al. Correlation between cyclooxygenase-2 expression and angiogenesis in human breast cancer. Clin Cancer Res. 2003;9(7):2651-6.
Shim V, Gauthier ML, Sudilovsky D, 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. 2003;63(10):2347-50.
Provenzano E, Hopper JL, Giles GG, et al. Histological markers that predict clinical recurrence in ductal carcinoma in situ of the breast: an Australian population-based study. Pathology. 2004;36(3):221-9.
Perrone G, Santini D, Vincenzi B, et al. COX-2 expression in DCIS: correlation with VEGF, HER-2/neu, prognostic molecular markers and clinicopathological features. Histopathology. 2005;46(5):561-8.
Benoit V, Relic B, Leval Xd X, et al. Regulation of HER-2 oncogene expression by cyclooxygenase-2 and prostaglandin E2. Oncogene. 2004;23(8):1631-5.
Cho MH, Yoon JH, Jaegal YJ, et al. Expression of cyclooxygenase-2 in breast carcinogenesis and its relation to HER-2/neu and p53 protein expression in invasive ductal carcinoma. Breast. 2006;15(3):390-8.
