ABSTRACT
The purpose of this study was to evaluate cyclooxygenase-2 (COX-2) expression in the successive steps of breast carcinogenesis and to determine its correlation with HER-2/neu and p53 expression in invasive ductal carcinomas of the breast. Immunohistochemical staining with anti-COX-2 antibody was performed in normal breast tissue, usual hyperplasia, ductal carcinoma in situ, and invasive ductal carcinoma. Expression of COX-2 in invasive ductal carcinoma was correlated with immunohistochemical expression of HER-2/neu and p53 protein. COX-2 expression was found to be progressively elevated along the continuum from normal breast tissue to invasive ductal carcinoma (P<0.001). COX-2 expression significantly correlated with p53 and HER-2/neu protein expression (P<0.05 and P<0.001). On multivariate analysis, only TNM stage and elevated COX-2 expression correlated with survival. Our results suggest that COX-2 may be involved in the carcinogenesis of the breast and may be an independent prognostic indicator in patients with invasive ductal carcinoma. HER-2/neu and p53 are likely to be involved in the regulation of COX-2 expression in invasive ductal carcinomas of the breast.
Subject(s)
Breast Neoplasms/metabolism , Carcinoma, Ductal, Breast/metabolism , Cyclooxygenase 2/biosynthesis , Gene Expression Regulation, Neoplastic/physiology , Receptor, ErbB-2/biosynthesis , Tumor Suppressor Protein p53/biosynthesis , Adult , Aged , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/mortality , Carcinoma, Ductal, Breast/pathology , Disease Progression , Female , Humans , Immunohistochemistry , Middle Aged , Neoplasm Staging , Proportional Hazards Models , Survival AnalysisABSTRACT
This study evaluated the relation of Tc-99m sestamibi (MIBI) uptake and washout in untreated breast cancer with immunohistochemically determined angiogenesis and P-glycoprotein expression. Thirty-one patients with untreated breast cancer were studied prospectively. Tc-99m MIBI scintigraphy and immunohistochemical analyses of angiogenesis and P-glycoprotein expression were used to evaluate surgically removed tumor tissues. Anterior and both lateral planar images were acquired 10 and 180 minutes after intravenous injection of 740 MBq (20 mCi) Tc-99m MIBI. The tumor-to-normal breast ratio (T:N) and washout index (early T:N - late T:N divided by early T:N) were calculated. A significant correlation was found between angiogenesis and T:N at early and late images. Pearson's correlation coefficients and probability values were r = 0.54, P = 0.002 at early images and r = 0.47, P = 0.008 at late images. The T:N of both early and late images were not different among different groups of P-glycoprotein expression (P = 0.367 and P = 0.113, respectively), although the washout index was significantly different among the groups (P = 0.001). A strong correlation was found between the washout index and P-glycoprotein expression (r = 0.67, P < 0.01). Double-phase scintimammography to assess the early tumoral uptake and washout of Tc-99m MIBI can be used as a simple functional test for in vivo imaging of tumoral angiogenesis and P-glycoprotein expression in patients with untreated breast cancer.
