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PMID: 14735188 Published · ppublish English Comparative Study Journal Article

COX-2 expression is associated with an aggressive phenotype in ductal carcinoma in situ.

British journal of cancer ·Vol. 90 ·No. 2 ·2004-01-26 ·Pages 423-9

Boland GP, Butt IS, Prasad R, Knox WF, Bundred NJ

Abstract

Cyclooxygenase type-2 (COX-2) is overexpressed in malignant tumours including breast cancers, though the mechanism of upregulation is unclear. This study aimed to determine COX-2 expression in ductal carcinoma in situ (DCIS) in comparison to invasive breast cancer (IBC) and normal breast, and also to investigate the relationship of COX-2 expression with HER-2 expression, oestrogen receptor (ER), tumour grade and cellular proliferation (Ki67) in DCIS. Cyclooxygenase type-2, HER-2, ER and Ki67 expression were determined by immunohistochemistry on paraffin tissue sections of DCIS (n=187), IBC (n=65) and normal breast reduction tissue (n=60). Cyclooxygenase type-2 expression in DCIS (67%, P<0.001) and IBC (63%, P<0.001) was significantly greater than in normal breast (23%). There was no difference in COX-2 expression level between DCIS and IBC (P=0.87) or between normal breast from reduction mammoplasty tissue and normal breast ducts around DCIS (22%, P=0.29). In DCIS, COX-2 expression was associated with higher cellular proliferation rates (P<0.0001), nuclear grade (P=0.003), with ER negativity (P=0.003) and with HER-2 positivity (P<0.0001). Cyclooxygenase type-2 expression is upregulated in in situ breast cancer and is associated with surrogate markers of an aggressive DCIS phenotype including nonoestrogen-regulated signalling pathways. Cyclooxygenase type-2 inhibition may potentially prevent the development of ER-positive and ER-negative breast cancers.

MeSH Terms
Adult Breast Neoplasms/enzymology,genetics,pathology Carcinoma, Intraductal, Noninfiltrating/enzymology,genetics,pathology Cell Division Cyclooxygenase 2 Cyclooxygenase 2 Inhibitors Cyclooxygenase Inhibitors/therapeutic use Female Gene Expression Regulation, Neoplastic Humans Isoenzymes/biosynthesis,pharmacology Membrane Proteins Middle Aged Neoplasm Invasiveness Phenotype Prognosis Prostaglandin-Endoperoxide Synthases/biosynthesis,pharmacology Receptors, Estrogen/analysis Retrospective Studies Signal Transduction Up-Regulation
Chemicals
Cyclooxygenase 2 Inhibitors Cyclooxygenase Inhibitors Isoenzymes Membrane Proteins Receptors, Estrogen Cyclooxygenase 2 PTGS2 protein, human Prostaglandin-Endoperoxide Synthases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Boland G P
Academic Department of Surgery, University Hospital of South Manchester, Southmoor Road, Manchester M23 9LT, UK.
Butt I S
Prasad R
Knox W F
Bundred N J
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Article Info
Journal
British journal of cancer
Abbr.
Br J Cancer
ISSN
0007-0920
DOI
10.1038/sj.bjc.6601534
Published
2004-01-26
Pages
423-9
Language
English
Region
England
NLM ID
0370635
PMCID
PMC2409574
Subset
IM
External Links
PubMed source DOI: 10.1038/sj.bjc.6601534 PMC Full Text View journal details
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