Cyclo-oxygenase 2 Expression is Associated with Angiogenesis and Lymph Node Metastasis in Human Breast Cancer

Overview

Journal J Clin Pathol

Specialty Pathology

Date 2002 May 31

PMID 12037025

Citations 78

Authors

C Costa

R Soares

J S Reis-Filho

D Leitao

I Amendoeira

F C Schmitt

Affiliations

Soon will be listed here.

Abstract

Aims: Cyclo-oxygenases 1 and 2 (COX-1 and COX-2) are key enzymes in prostaglandin biosynthesis. COX-2 is induced by a wide variety of stimuli, and present during inflammation. COX-2 overexpression has been observed in colon, head and neck, lung, prostate, stomach, and breast cancer. In colon and gastric cancer, COX-2 expression was associated with angiogenesis. The aim of this study was to determine the relation between COX-2 expression and angiogenesis in breast cancer, and to correlate the expression of this enzyme with classic clinicopathological parameters.

Methods: COX-2 expression was investigated by immunohistochemistry and western blotting analysis. The expression of COX-2 was then related to age, histological grade, nodal status, oestrogen receptor status, p53 expression,c-erb-B2 overexpression, mitotic counts, MIB-1 labelling index, apoptotic index, sialyl-Tn expression, transforming growth factor alpha expression, microvessel density, and disease free survival in 46 patients with invasive ductal breast carcinoma.

Results: By means of immunohistochemistry, COX-2 expression was detected in eight of the 46 carcinomas studied. Western blotting showed COX-2 protein expression in the same breast tumours, but not in normal adjacent tissues. The density of microvessels immunostained with anti-F-VIII related antigen was significantly higher in patients with COX-2 expression than in those without expression (p = 0.03). In addition, COX-2 was significantly associated with the presence of sialyl-Tn expression (p = 0.02), lymph node metastasis (p = 0.03), a high apoptotic index (p = 0.03), and a short disease free survival (p = 0.03) in univariate analyses.

Conclusions: These data suggest that COX-2 expression is associated with angiogenesis, lymph node metastasis, and apoptosis in human breast cancer. Moreover, these results warrant further studies with larger series of patients to confirm the association with short disease free survival in patients with breast cancer.

Citing Articles

Celecoxib inhibits NLRP1 inflammasome pathway in MDA-MB-231 Cells.

Arzuk E, Birim D, Armagan G Naunyn Schmiedebergs Arch Pharmacol. 2024; 397(11):9191-9202.

PMID: 38990306 PMC: 11522188. DOI: 10.1007/s00210-024-03286-2.

The Antioxidant Potential and Anticancer Activity of Ethanolic Extract against Triple-Negative Breast Cancer Cells.

Wehbe N, Badran A, Baydoun S, Al-Sawalmih A, Maresca M, Baydoun E Antioxidants (Basel). 2024; 13(6).

PMID: 38929164 PMC: 11200955. DOI: 10.3390/antiox13060726.

Exploring the Role of Apigenin in Neuroinflammation: Insights and Implications.

Charriere K, Schneider V, Perrignon-Sommet M, Lizard G, Benani A, Jacquin-Piques A Int J Mol Sci. 2024; 25(9).

PMID: 38732259 PMC: 11084463. DOI: 10.3390/ijms25095041.

Canine Mammary Cancer: State of the Art and Future Perspectives.

Vazquez E, Lipovka Y, Cervantes-Arias A, Garibay-Escobar A, Haby M, Queiroga F Animals (Basel). 2023; 13(19).

PMID: 37835752 PMC: 10571550. DOI: 10.3390/ani13193147.

The use of Xuanbai Chengqi decoction on monkeypox disease through the estrone-target AR interaction.

Jiao Y, Shi C, Sun Y Front Microbiol. 2023; 14:1234817.

PMID: 37808322 PMC: 10553791. DOI: 10.3389/fmicb.2023.1234817.

References

Gustafsson J . Estrogen receptor beta--a new dimension in estrogen mechanism of action. J Endocrinol. 1999; 163(3):379-83. DOI: 10.1677/joe.0.1630379. View

Schrey M, Patel K . Prostaglandin E2 production and metabolism in human breast cancer cells and breast fibroblasts. Regulation by inflammatory mediators. Br J Cancer. 1995; 72(6):1412-9. PMC: 2034098. DOI: 10.1038/bjc.1995.523. View

Liu S, Edgerton S, Moore 2nd D, Thor A . Measures of cell turnover (proliferation and apoptosis) and their association with survival in breast cancer. Clin Cancer Res. 2001; 7(6):1716-23. View

Williams C, DuBois R . Prostaglandin endoperoxide synthase: why two isoforms?. Am J Physiol. 1996; 270(3 Pt 1):G393-400. DOI: 10.1152/ajpgi.1996.270.3.G393. View

Soares R, Pereira M, Silva C, Amendoeira I, Wagner R, Ferro J . Expression of TGF-alpha and EGFR in Breast Cancer and its Relation to Angiogenesis. Breast J. 2001; 6(3):171-177. DOI: 10.1046/j.1524-4741.2000.98046.x. View

FULTON A, Heppner G . Relationships of prostaglandin E and natural killer sensitivity to metastatic potential in murine mammary adenocarcinomas. Cancer Res. 1985; 45(10):4779-84. View

Risau W . Mechanisms of angiogenesis. Nature. 1997; 386(6626):671-4. DOI: 10.1038/386671a0. View

Hixson L, Alberts D, Krutzsch M, Einsphar J, Brendel K, GROSS P . Antiproliferative effect of nonsteroidal antiinflammatory drugs against human colon cancer cells. Cancer Epidemiol Biomarkers Prev. 1994; 3(5):433-8. View

Hida T, Yatabe Y, Achiwa H, Muramatsu H, Kozaki K, Nakamura S . Increased expression of cyclooxygenase 2 occurs frequently in human lung cancers, specifically in adenocarcinomas. Cancer Res. 1998; 58(17):3761-4. View

10.

Elston C, Ellis I . 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. DOI: 10.1111/j.1365-2559.1991.tb00229.x. View

11.

Tucker O, Dannenberg A, Yang E, Zhang F, Teng L, Daly J . Cyclooxygenase-2 expression is up-regulated in human pancreatic cancer. Cancer Res. 1999; 59(5):987-90. View

12.

Yip-Schneider M, Barnard D, Billings S, Cheng L, Heilman D, Lin A . Cyclooxygenase-2 expression in human pancreatic adenocarcinomas. Carcinogenesis. 2000; 21(2):139-46. DOI: 10.1093/carcin/21.2.139. View

13.

Prescott S, Fitzpatrick F . Cyclooxygenase-2 and carcinogenesis. Biochim Biophys Acta. 2000; 1470(2):M69-78. DOI: 10.1016/s0304-419x(00)00006-8. View

14.

Simon L . Role and regulation of cyclooxygenase-2 during inflammation. Am J Med. 1999; 106(5B):37S-42S. DOI: 10.1016/s0002-9343(99)00115-1. View

15.

Marinho A, Soares R, Ferro J, Lacerda M, Schmitt F . Angiogenesis in breast cancer is related to age but not to other prognostic parameters. Pathol Res Pract. 1997; 193(4):267-73. DOI: 10.1016/S0344-0338(97)80003-9. View

16.

Bennett A, Charlier E, McDonald A, Simpson J, Stamford I, ZEBRO T . Prostaglandins and breast cancer. Lancet. 1977; 2(8039):624-6. DOI: 10.1016/s0140-6736(77)92496-5. View

17.

Gilhooly E, Rose D . The association between a mutated ras gene and cyclooxygenase-2 expression in human breast cancer cell lines. Int J Oncol. 1999; 15(2):267-70. View

18.

Kargman S, ONeill G, Vickers P, Evans J, Mancini J, Jothy S . Expression of prostaglandin G/H synthase-1 and -2 protein in human colon cancer. Cancer Res. 1995; 55(12):2556-9. View

19.

Hanif R, Pittas A, Feng Y, Koutsos M, Qiao L, Staiano-Coico L . Effects of nonsteroidal anti-inflammatory drugs on proliferation and on induction of apoptosis in colon cancer cells by a prostaglandin-independent pathway. Biochem Pharmacol. 1996; 52(2):237-45. DOI: 10.1016/0006-2952(96)00181-5. View

20.

ONeill G, Ford-Hutchinson A . Expression of mRNA for cyclooxygenase-1 and cyclooxygenase-2 in human tissues. FEBS Lett. 1993; 330(2):156-60. DOI: 10.1016/0014-5793(93)80263-t. View