Analysis of cyclooxygenase-2 expression in human breast cancer: high throughput tissue microarray analysis

Abstract

Purpose: The objective of this study was to evaluate breast carcinomas for the expression of cyclooxygenase-2 (Cox-2) using a tissue microarray (TMA) and to determine its clinical and prognostic relevance.

Methods: We analyzed Cox-2 expression in 600 samples from 200 breast carcinomas immunohistochemically performing TMA technology and semiquantitative analysis. Results were correlated with various clinicopathological variables and follow-up data. Expression of estrogen receptor, progesterone receptor, Ki-67, and Her-2/neu-oncogene was analyzed and correlated with Cox-2 status.

Results: We observed a moderate or strong cytoplasmic staining for Cox-2 in 78 (40.6%) of breast carcinomas. Increased Cox-2 expression corresponded to higher pT stage ( P=0.038), amplification of Her-2/neu ( P=0.032), lymphovascular invasion ( P=0.006), a high MIB-1 labeling index (LI) ( P<0.001), and histological grading ( P=0.013). We also observed an inverse relationship between strong Cox-2 expression and estrogen and progesterone receptor content of tumors ( P=0.037 and P=0.010). However, we could not demonstrate a significant association between Cox-2 staining and overall survival or disease free survival time.

Conclusions: These results suggest that Cox-2 expression is significantly associated with less differentiated and more aggressive breast carcinomas and might therefore be a useful prognostic indicator as well as a target for therapy.

Fig. 1.

Tissue microarray block

Fig. 2A-F.

Breast cancer samples of TMA with immunohistochemical expression of A Cox-2, B estrogen receptor, C progesterone receptor, D MIB-1), E Her-2/neu (magnification ×100); F in situ hybridization for Her-2/neu

Fig. 3A-H.

Association between Cox-2 and clinicopathological features in patients with primary breast cancer (n = 178). A Cox-2 expression and pT-stage; P=0.002; B Cox-2 expression and lymphovascular invasion; P=0.003; C Cox-2 expression and MIB-1 labeling index (LI ≤20% vs LI >20%); P=0.010; D Cox-2 expression and Her-2/neu amplification; NS; P=0.168; E Cox-2 expression and histological differentiation (grading); P=0.038; F Cox-2 expression and expression of estrogen receptor; NS (P=0.080); G Cox-2 expression and expression of progesterone receptor; P=0.023; H Cox-2 expression and pN status; P=0.041

Fig 4A,B.

Survival distribution functions (OS and DFST) in patients with primary breast cancer (n = 178). A Overall survival (OS) in patients with Cox-2-negative (n = 94) vs patients with Cox-2-positive (n = 66) tumors; NS (P=0.227); B Disease-free survival time (DFST) in patients with Cox-2-negative (n = 82) vs patients with Cox-2-positive (n = 57) tumors; NS (P=0.525)