Stromal, rather than epithelial cyclooxygenase-2 (COX-2) expression is associated with overall survival of breast cancer patients

Justyna Urban,Agata Stanek-Widera,Grzegorz Szatkowski,Łukasz Kuźbicki,Barbara W Chwirot,Dariusz Lange

doi:10.1186/1471-2407-14-732

Abstract

BackgroundPrognostic value of enhanced COX-2 expression in breast cancer has been controversial for a long time. The opinions vary widely between studies. Moreover, significant majority of studies considered only COX-2 expression in cancer epithelial cells.MethodsWe examined the prognostic value of COX-2 expression in both epithelial and stromal cells using three different antibodies and three algorithms of immunohistochemical scoring and categorizing the tumours into COX-2 overexpressing groups.ResultsOur results demonstrate that COX-2 expression in stromal cells is independent prognostic factor indicating worse overall survival of patients. Such a result was obtained using each of the three antibodies and two of the algorithms used for evaluations of COX-2 expression levels. We also show that immunohistochemical assessment of the prognostic value of COX-2 expression in cancer epithelial cells depends to a large extent on a combination of primary antibodies and algorithms used for determination of the COX-2 over-expressing tumours.ConclusionsOur results indicate that stromal expression of COX-2 is independent prognostic parameter relatively insensitive to variations in sensitivity of antibodies used for its determination. Wide scatter of the published results concerning prognostic value of COX-2 expression in breast cancer tissues seems to be due to a large extent to multitude of antibodies and scoring algorithms used by different groups.

Highlights

Prognostic value of enhanced COX-2 expression in breast cancer has been controversial for a long time
Several epidemiologic studies indicate that regular use of non-steroidal anti-inflammatory drugs (NSAIDs) which inhibit COX-2 reduces incidence of at least some types of human cancers like sporadic and familial colon cancer, pancreatic cancer, melanoma and breast cancer
The detection sensitivity of the antibodies was assessed by comparing percentage fractions of the COX-2 positive cells detected in tissue sections of the same lesions

Summary

Introduction

Prognostic value of enhanced COX-2 expression in breast cancer has been controversial for a long time. Increased expression of cyclooxygenase-2 (COX-2) has been reported for many types of human cancer including breast cancer. Several epidemiologic studies indicate that regular use of non-steroidal anti-inflammatory drugs (NSAIDs) which inhibit COX-2 reduces incidence of at least some types of human cancers like sporadic and familial colon cancer, pancreatic cancer, melanoma and breast cancer (see for instance [1,2]). A role of enhanced COX-2 expression in breast cancer development and progression has not been fully elucidated yet and the literature data on prognostic usefulness of COX-2 for the breast cancer are inconsistent. Other groups reported that immunohistochemically detected COX-2 expression did not provide prognostic information [17,18,19,20,21]

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Discussion

Conclusion