Abstract
4276
Background Cyclooxygenase-2 (COX - 2) is an inducible enzyme overexpressed in certain malignancies, particularly in colon and breast carcinoma. Its presence in precancerous tissue such as breast atypical ductal hyperplasia may indicate that selective COX-2 inhibitors may be a reasonable component for primary prevention in people with such precancerous risk factors for the development of breast carcinoma. Also, by comparing our results with prior results of COX-2 expression that we had studied in invasive cancer, we hypothesize that COX-2 may be upregulated early in the tumorigenesis process. Methods Twenty-eight patients with breast atypical ductal hyperplasia (ADH) who had archival tissue available between 1993 - 2003 were examined. A specific COX-2 anti-human polyclonal antibody was used as the immunohistochemical assay in these paraffin embedded archival specimens. A scoring system was then performed with each individual subject with respect to the staining intensity (0-3+) and the percentage of positive cells for the COX-2 antibody. The positive specimens were then compared to a negative control for validity. In addition, we examined Her-2/neu and p53 in these specimens. Results Using the immunohistochemical scoring system (IHC); 3/28 (10.7%) of atypical ductal hyperplasia exhibited mild to moderate staining for COX-2. (1+) In the positive specimens, 80 % of all the ADH cells expressed the COX - 2 antibody. In our other historical data, 18/29 (62.1%) of in situ and 42/60 (70%) of invasive, early stage, node-negative patients exhibited moderate to intense staining for COX-2. In addition, no patients with atypical ductal hyperplasia exhibited either Her-2/neu or p53 overexpression. Conclusion Of the specimens obtained, 10.7% of the atypical ductal hyperplasia in breast tissue had demonstrated some expression of COX-2. As the stage of cancer increases, so does the level of COX-2 expression. There may be a possibility that COX-2 is upregulated early in tumorigenesis. This may play a future role in primary prevention via selective COX-2 inhibition for those patients who demonstrate COX-2 activity early in breast biopsy specimens.
[Proc Amer Assoc Cancer Res, Volume 46, 2005]